Materiały źródłowe

• #1 Amyotrophic Lateral Sclerosis (ALS): What It Is & Symptoms

  https://my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als

  Amyotrophic lateral sclerosis, or ALS, is a neurodegenerative disease that targets the nerve cells (neurons) in your brain and spinal cord. It affects your muscle control. Symptoms worsen over time. […] Researchers dont know what causes amyotrophic lateral sclerosis. They believe its a combination of the following factors: […] About 70% of familial cases and 5% to 10% of sporadic cases involve gene changes. Theyre most often in the C9orf72, SOD1, TARDBP and FUS genes. There are more than 40 related genes. […] Exposure to toxins (like lead or mercury), viruses or trauma may also play a role. […] Some types of amyotrophic lateral sclerosis are genetic. You can inherit genetic changes that cause ALS from your biological parents. Inherited ALS isnt common, though. Sometimes, genetic changes happen randomly, without a history in your biological family. […] Theres no proven way to prevent ALS. Research is ongoing to learn more about the causes and risk factors to help create prevention methods in the future.

• #1 Causes/Inheritance – Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/amyotrophic-lateral-sclerosis/causes-inheritance

  About 5-10% of ALS is familial meaning it arises in families in which there is a history of ALS. A number of genes associated with ALS have been identified or at least mapped to a specific region of a chromosome. […] The other 90-95% of ALS is sporadic, meaning it occurs without a family history (in other words, „sporadically”). There appear to be genetic variations that influence one’s susceptibility to sporadic ALS, even if they do not necessarily cause the disease by themselves. Additionally, some of the same genes identified to cause familial ALS have been found in patients with sporadic ALS. […] The only established risk factors for ALS are age and family history. […] Below, you will find an examination of possible causes of both sporadic and familial ALS currently under investigation by MDA researchers.

• #1 Amyotrophic Lateral Sclerosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556151/

  Over 120 genes have been implicated in ALS. […] A prevailing thought is that the accumulation of abnormal proteins due to aberrant RNA processing is involved in the development of ALS. […] The risk variables include sports with a high incidence of concussions, military jobs, smoking, exposure to heavy metals (lead, manganese), pesticides, neurotoxins (cyanobacteria), and electromagnetic fields.

• #1 What is ALS? | Eleanor and Lou Gehrig ALS Center

  https://www.alscenter.cuimc.columbia.edu/patient-care/what-als

  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily involves the degeneration of motor neurons in the brain and spinal cord. […] In most cases, the cause is unknown, but in about 10 percent of patients, the disease is familial (fALS), which means that it is associated with a genetic mutation inherited from one or the other parent in a dominant manner. […] Over 30 different genes have been identified in which mutation(s) cause ALS and over 60 percent of ALS cases are caused by a mutation in one of these known ALS genes. […] The most common known cause of ALS is a mutation in a gene called C9orf72, which accounts for nearly half of all cases of familial ALS, and about 10 percent of sporadic disease. […] In more than 60 percent of familial cases, and upwards of 15 percent of sporadic ALS patients, a mutation is found in a known ALS gene, many of which have been identified in the last 10 years.

• #1 Amyotrophic Lateral Sclerosis (ALS): Causes and Symptoms

  https://www.aarp.org/health/conditions-treatments/amyotrophic-lateral-sclerosis-als/

  ALS is a progressive disease with no cure. […] It is also rare: About 30,000 people in the United States have it. […] But why these cells start dying? Honestly, we dont fully understand, says Jeffrey Rothstein, M.D., director of the Robert Packard Center for ALS Research at Johns Hopkins Medicine. […] Even though its not clear what causes ALS, certain people may be more likely to get it. […] A small proportion of the people who get ALS about 1 in 10 were born with a gene mutation that caused the disease. […] In most cases, just inheriting the gene from one parent is enough to ensure that a person will develop whats called familial, or genetic, ALS. […] About 25 to 40 percent of people with familial ALS have defects in a gene called C9orf72. […] Another 12 to 20 percent of familial cases have ALS due to a defect in a gene called SOD1.

• #1 Amyotrophic lateral sclerosis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-3

  20% of cases with autosomal dominant FALS and 2% of patients with SALS show mutations in the Copper-Zinc superoxide dismutase (SOD1) gene. Mutations in the gene are thought to cause disease through a toxic gain of function rather than causing impairment of the antioxidant function of the SOD1 enzyme. Other genes causing familial MND include alsin (ALS2), senataxin (ALS4), Vesicle associated membrane protein (VAPB, ALS8), Angiogenin and a mutation in the p150 subunit of dynactin (DCTN1). Recently, mutations in TARDBP gene (encoding the TAR-DNA binding protein TDP-43) located on chromosome 1p36.22 have been linked to familial and sporadic ALS. Several other gene mutations have been identified in sporadic cases which may increase susceptibility to ALS, such as mutations in the KSP repeat region in the NEFH gene (encoding neurofilament heavy subunit), apolipoprotein E 4 genotype (APOE), decreased expression of EAAT2 protein and alterations in the Vascular endothelial growth factor (VEGF) gene to name a few.

• #1 Amyotrophic Lateral Sclerosis (ALS) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/amyotrophic-lateral-sclerosis

  ALS is characterized by the gradual degeneration and death of motor neurons, which are the nerve cells in the brain and spinal cord that control voluntary muscles, such as those involved in walking and talking. […] The exact cause of ALS is unknown. However, it is believed that a combination of genetic and environmental factors contributes to the development of the disease. […] In 90% of cases, ALS is sporadic, meaning it occurs without known risk factors or a family history of the condition. […] In about 10%-15% of cases, ALS is familial. Roughly 70% of familial ALS and 15% of sporadic ALS have mutations in known ALS genes, including SOD1, FUS, TARDBP, C9ORF72, and ATXN2, among others. It is important to note that presence of certain gene mutations doesn’t necessarily mean that someone will develop ALS. […] Although the exact cause of ALS is not known, certain factors may increase a person’s risk. These include age, male sex, genetic risk factors, lifestyle risk factors, occupational risk factors, and environmental risk factors.

• #1 Amyotrophic Lateral Sclerosis (ALS) Causes | ALS News TodayEnvelope icon

  https://alsnewstoday.com/causes-of-als/

  The exact cause of amyotrophic lateral sclerosis (ALS) is largely unknown, but a number of factors including genetics, environmental exposures, and lifestyle habits have been linked to an increased risk of ALS. […] There is strong evidence that an individual’s genetics have an impact on the risk of developing ALS. Mutations in more than a dozen genes have been definitively linked with ALS, and many more genes have shown potential associations with disease risk. […] ALS can broadly be divided into two types: familial, meaning the disease affects more than one person in a family, and sporadic, when there’s no family history. […] Importantly, most ALS-associated mutations have incomplete penetrance and genetic pleiotropy. In other words, just because a person has a certain mutation does not mean that the individual is guaranteed to develop ALS; other factors also play a role.

• #1 Amyotrophic Lateral Sclerosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556151/

  Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is the most common motor neuron disease (MND) in a group of illnesses that involve both upper and lower motor neurons. […] With both sporadic and familial forms, a single and precise etiology of amyotrophic lateral sclerosis is lacking. There are multiple genetic and environmental proposed causes. […] The etiology of ALS is unknown. Numerous possible genetic and sporadic possibilities are suggested. […] A single and precise etiology governing ALS is lacking. The possible mechanisms described in the literature are genetic mutations, oxidative stress, excitotoxicity, mitochondrial and proteasomal dysfunctions, altered synaptic function, disturbed axonal transport, and neuroinflammation. […] It appears that ALS develops as a result of the interaction between both genetic and environmental factors.

• #1 Amyotrophic Lateral Sclerosis (ALS)

  https://www.webmd.com/brain/understanding-als-basics

  Immune system problems. Your immune system protects your body from foreign invaders such as bacteria and viruses. Microglia are the main type of immune cell in your brain. They destroy germs and damaged cells. With ALS, microglia might also destroy healthy motor neurons. […] Mitochondria problems. Mitochondria are the parts of your cells where energy is made. A problem with them might lead to amyotrophic lateral sclerosis or make an existing case worse. […] Oxidative stress. Your cells use oxygen to make energy. Your body may form some of this oxygen into toxic substances called free radicals, which can damage cells. The medication edaravone (Radicava) is an antioxidant that can help control these free radicals.

• #1 Amyotrophic lateral sclerosis (ALS): Causes, symptoms, and treatment

  https://www.medicalnewstoday.com/articles/281472

  The exact cause is unclear, but environmental and genetic factors may be involved. […] Research has focused on genetics and environmental factors as possible causes of ALS. […] About 20-40% of familial ALS cases, and a small number of sporadic cases, stem from a difference in the C9ORF72 gene. […] And 12-20% of familial cases result from mutations in the SOD1 gene, which is key to the functioning of motor neurons and other cells. […] Other possible causes of ALS include: Disorganized immune response: The immune system may attack some of the body’s cells, possibly killing nerve cells. […] Chemical imbalance: People with ALS often have higher levels of glutamate, a chemical messenger in the brain, near the motor neurons. Glutamate in high quantities can be toxic to nerve cells. […] Mishandling of proteins: If nerve cells do not process proteins correctly, the resulting atypical proteins might accumulate and cause the nerve cells to die. […] One study reports that military personnel deployed in the Gulf region during the 1991 war were more likely to develop ALS than those deployed elsewhere. […] However, there is no conclusive evidence that any lifestyle changes reduce the risk of developing ALS.

• #1 ALS Pathophysiology – ALS Causes | ALS Pathways

  https://www.alspathways.com/hcp/rethinking-als/

  While our knowledge of the pathogenesis of ALS remains incomplete, new and exciting research continues to uncover information about the pathophysiology and underlying causes of ALS. […] Research suggests many factors may contribute to motor neuron cell deterioration, including: oxidative stress, defective glutamate metabolism, mitochondrial dysfunction, genetic variations, apoptosis, cytoskeletal protein defects preventing normal cell movement and division, autoimmune dysfunction, inflammatory responses.

• #1 ALS – Wikipedia

  https://en.wikipedia.org/wiki/ALS

  Most cases of ALS (about 90-95%) have no known cause, and are known as sporadic ALS. […] However, both genetic and environmental factors are believed to be involved. […] The remaining 5-10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). […] It is not known what causes sporadic ALS, hence it is described as an idiopathic disease. […] Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. […] The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. […] A multi-step liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. […] The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. lead and mercury), chemicals (e.g. pesticides and solvents), electric shock, physical injury (including head injury), and smoking (in men more than women).

• #1 Amyotrophic Lateral Sclerosis (ALS) Causes | ALS News TodayEnvelope icon

  https://alsnewstoday.com/causes-of-als/

  Smoking cigarettes is one of the most well-established lifestyle risk factors for ALS. Studies suggest that the risk of ALS is increased by more than 40% among people who have ever smoked cigarettes, compared to those who have never smoked. […] Some lifestyle habits, such as smoking and excessive exercise, have been linked to an increased risk of developing amyotrophic lateral sclerosis (ALS). However, lifestyle choices alone are not sufficient to cause the disease — most people who smoke or exercise a lot will never develop ALS. Other factors including genetics and environmental exposures also affect an individual’s risk of developing ALS. […] A person’s genetics can influence the risk of developing amyotrophic lateral sclerosis (ALS), and mutations in more than 30 genes have been linked with ALS. However, genetics alone are not usually enough to cause ALS — just because someone has a disease-associated mutation does not guarantee that the individual will develop ALS. An interaction between mutations and factors like lifestyle habits and environmental exposures are thought to influence the risk of ALS.

• #1 About Amyotrophic Lateral Sclerosis (ALS) | National ALS Registry | CDC

  https://www.cdc.gov/als/abouttheregistrymain/about-amyotrophic-lateral-sclerosis-als.html

  No one knows what causes most cases of ALS. […] No cause has been found for most cases of ALS. In the future, scientists may find that many factors together cause ALS. […] Health studies have not found definite environmental factors that are linked with either ALS or other MNDs. […] Some studies suggested a possible link with exposure to heavy metals (e.g., lead and mercury). […] Other studies suggested a link with exposure to trace elements, solvents, radiation, and agricultural chemicals. […] About 510% of ALS cases occur within families. This is called familial ALS and it means that two or more people in a family have ALS. These cases are caused by several inherited factors. The most common is in a gene called SOD1. […] Familial ALS is found equally among men and women.

• #1 Who Gets ALS?

  https://www.webmd.com/brain/who-gets-als

  Mutations on this gene appear in about 20% of familial cases and 1% to 5% of sporadic ones. Its unclear how the mutations lead to ALS. […] Scientists are also looking at whether things in the environment such as chemicals and other agents can raise your chances of getting ALS. […] Smoking is believed to be the only probable factor that may raise your chances for ALS. […] Lead and other chemicals may be linked to ALS, but no single agent has been consistently found to be a cause. […] Studies have found that military veterans, especially those deployed during the Gulf War in 1991, have a greater chance of ALS. […] The most famous person to have ALS was Lou Gehrig, the baseball player who died from it. […] Several lines of work — including sports, cockpit, construction, farm, hairdressing, lab, veterinary, and welding, among many others — have been reported to carry a higher chance of ALS. […] Clusters of ALS cases have been reported on the Pacific island of Guam and in the Kii Peninsula in Japan, which have rates 50 to 100 times higher than other parts of the world.

• #1 Amyotrophic Lateral Sclerosis (ALS) Causes | ALS News TodayEnvelope icon

  https://alsnewstoday.com/causes-of-als/

  If an individual with ALS does not have a family history of the disease, it’s referred to as sporadic ALS, meaning isolated or without clear patterns. Genetics are thought to play a role in determining disease risk in sporadic cases, though the precise effects still are incompletely understood. […] While the genetic basis of ALS is relatively well established, gene mutations are not the sole determinants of disease risk. The likelihood of someone developing the disease is thought to result from the interaction between genetic alterations and environmental and lifestyle factors. […] Studies have shown that a person’s experiences, habits, and career may influence the risk of ALS. […] Some studies have suggested that people with a history of electric shock and/or exposure to electromagnetic fields (EMFs) are more likely to develop ALS.

• #1 Risk factors for amyotrophic lateral sclerosis | CLEP

  https://www.dovepress.com/risk-factors-for-amyotrophic-lateral-sclerosis-peer-reviewed-fulltext-article-CLEP

  According to an evidence-based medicine analysis, smoking is the only probable risk factor for ALS. […] The most investigated relationship between dietary factors and ALS is the inverse association between higher intake of antioxidants and a lower risk of ALS. […] There is a strong clinical impression that ALS patients have a higher level of physical fitness and lower body mass index (BMI) than average. […] Workers in various occupations with seemingly disparate exposures have been reported to be potentially at altered risk of ALS, including athletes, carpenters, cockpit workers, construction workers, electrical workers, farm workers, hairdressers, house painters, laboratory technicians, leather workers, machine assemblers, medical service workers, military workers, nurses, power production plant workers, precision metal workers, programmers, rubber workers, shepherds, tobacco workers, veterinarians, and welders.

• #1 Amyotrophic Lateral Sclerosis (ALS) | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als

  Other studies are working to identify additional genes that may cause or put a person at risk for either familial or sporadic ALS. […] A large-scale collaborative research effort supported by NINDS, other NIH institutes, and several public and private organizations is analyzing genetic data from thousands of individuals with ALS to discover new genes involved in the disease. […] Additionally, researchers are looking at the potential role of epigenetics in ALS development. […] NINDS supports research on the development of biomarkersbiological measures of a disease. […] ALS biomarkers can help identify the rate of progression and the effectiveness of current and future therapies.

• #1 An Overview of Causes and Risk Factors for ALS

  https://www.neurologylive.com/view/an-overview-of-causes-and-risk-factors-for-als

  Finding environmental risk factors is much trickier because, although the genome is vast, it is a finite thing, and we know what we are testing. […] To make a point on that, Jinsy mentioned that military service during times of conflict is fairly clearly a risk factor for ALS, in the United States at least. […] Another factor to consider is that, for something we think might be a risk factor, the way we interpret it can be biased.

• #1

  https://www.feinberg.northwestern.edu/research/podcast/what-causes-als-with-robert-kalb-md.html

  The good news is that we’ve learned much more about the disease over the past decades. […] The key here is to understand the underlying basic biology that’s going wrong in motor neurons and cells that are supporting them and intervene. […] I’m quite sure that at some point there will be a pill, you take the pill in the morning, once a day, and the disease never progresses. […] There’s a childhood disease called spinal muscular atrophy. It’s a childhood motor neuron disease. Over the past 20 years we’ve identified with a genetic abnormality is in spinal muscular atrophy. […] Most individuals who have ALS have a sporadic form of disease, which means that there’s no clear genetic cause and about 10 or 15 percent, there’s a clear single gene which is mutated that causes the disease and you can track it through a family.

• #1 The mystery of why some people develop ALS

  https://www.bbc.com/future/article/20230825-the-mystery-of-why-some-people-develop-als

  Feldman also says that her team’s research looking at the combined risk from genetic and environmental factors „is a challenge” because they suspect that multiple genes tens and possibly even hundreds contribute to what they term the „polygenic risk profile” in ALS. […] The challenge, however, is funding for appropriate research. As well as working out how much of a contribution each gene or environmental factor might make, more studies are needed on how to apply any knowledge gained.

• #1 Amyotrophic lateral sclerosis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-3

  The cause of ALS/MND is unknown although some genetic risk factors have been identified. Recent reviews on the role of environmental risk factors in the causation of ALS have concluded that there is no consistent association between a single environmental factor and risk of developing ALS. Most authors favour a hypothesis of complex genetic-environmental interaction as the causal factor for motor neuron degeneration. […] Putative exogenous risk factors associated with development of ALS investigated in case-control studies have been reviewed, and are summarised in Appendix 1. By applying an evidenced based approach, it was found that only smoking is likely to be associated with developing ALS, while other risk factors were weakly related. More recent case-control studies have estimated the relative risk (RR) of ALS of 0.81.67 in smokers compared to non-smokers, and an odds ratio (OR) of 1.6 independent of age, level of education and occupation.

• #1 Causes/Inheritance – Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/amyotrophic-lateral-sclerosis/causes-inheritance

  C9orf72-related ALS is the most common autosomal dominantly inherited form of familial ALS (34% of the cases in European population), together with SOD1-related ALS as described above. […] Genetic testing is available for many ALS-causing gene mutations. Genetic testing for specific ALS-causing mutations is most useful for establishing the diagnosis. […] Genetic testing can provide information about whether someone with ALS is eligible for these trials.

• #1 Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/amyotrophic-lateral-sclerosis

  The causes of the vast majority of ALS cases are still unknown. Investigators theorize that some individuals may be genetically predisposed to developing the disease but do so only after coming into contact with an environmental trigger. The interaction of genetics and environment may hold clues as to why some individuals develop ALS. […] Although the majority of ALS cases are sporadic, meaning there is no family history of the disease, about 10% of cases are familial, meaning the disease runs in the family. A common misconception is that only familial ALS is „genetic.” Actually, both familial and sporadic ALS can stem from genetic causes, and some people who have a diagnosis of sporadic ALS may carry ALS-causing genetic mutations that can be passed on to offspring. A genetic counselor can help people with ALS understand inheritance and any associated risks for family members.

• #1 What Is Amyotrophic Lateral Sclerosis (ALS)? | UC Health

  https://www.uchealth.com/en/conditions/als

  Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that is caused by the gradual breaking down of nerve cells in the spine and brain. This disease is known to progress to a point of death as vital bodily functions begin to fail over time. […] Amyotrophic lateral sclerosis (ALS) is a fatal type of motor neuron disease. It causes progressive degeneration of nerve cells in the spinal cord and brain. […] Experts do not know the cause of ALS. More recently, genetic causes are being seen as increasingly important. Research is also looking into possible environmental causes of ALS. […] Researchers are conducting studies to increase their understanding of genes that may cause the disease. They are also looking at the mechanisms that can trigger motor neurons to degenerate in ALS and approaches to stop the progress leading to cell death.

• #2 Amyotrophic Lateral Sclerosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556151/

  Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is the most common motor neuron disease (MND) in a group of illnesses that involve both upper and lower motor neurons. […] With both sporadic and familial forms, a single and precise etiology of amyotrophic lateral sclerosis is lacking. There are multiple genetic and environmental proposed causes. […] The etiology of ALS is unknown. Numerous possible genetic and sporadic possibilities are suggested. […] A single and precise etiology governing ALS is lacking. The possible mechanisms described in the literature are genetic mutations, oxidative stress, excitotoxicity, mitochondrial and proteasomal dysfunctions, altered synaptic function, disturbed axonal transport, and neuroinflammation. […] It appears that ALS develops as a result of the interaction between both genetic and environmental factors.

• #2 Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/amyotrophic-lateral-sclerosis

  The causes of the vast majority of ALS cases are still unknown. Investigators theorize that some individuals may be genetically predisposed to developing the disease but do so only after coming into contact with an environmental trigger. The interaction of genetics and environment may hold clues as to why some individuals develop ALS. […] Although the majority of ALS cases are sporadic, meaning there is no family history of the disease, about 10% of cases are familial, meaning the disease runs in the family. A common misconception is that only familial ALS is „genetic.” Actually, both familial and sporadic ALS can stem from genetic causes, and some people who have a diagnosis of sporadic ALS may carry ALS-causing genetic mutations that can be passed on to offspring. A genetic counselor can help people with ALS understand inheritance and any associated risks for family members.

• #2 Amyotrophic Lateral Sclerosis: Disease State Overview

  https://www.ajmc.com/view/amyotrophic-lateral-sclerosis-disease-state-overview

  Sporadic ALS has no known cause, but it may possibly be caused by immune system abnormalities, toxic exposure, mitochondrial dysfunction, or glutamate toxicity. […] The genes are loosely categorized by function: disturbance of distal terminal and motor neuron axon cytoskeletal dynamics, alteration of protein quality control and proteostasis, and disruption of RNA metabolism, stability, and function. […] In 1993, SOD1 was the first gene linked to ALS. […] Since then, more than 120 genetic variants, linked with ALS risk, have been identified. […] Of these, roughly 25 genes have been associated with sporadic ALS, familial ALS, or both. […] Chromosome 9 open reading frame 72 (C9orf72), FUS, SOD1, and TARDBP are the most common genes associated with ALS.

• #2 Amyotrophic lateral sclerosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis/

  Mutations in the C9orf72 gene account for 30 to 40 percent of familial ALS in the United States and Europe. […] The cause of sporadic ALS is largely unknown but probably involves a combination of genetic and environmental factors. […] Variations in many genes, including the previously mentioned genes involved in transmission of nerve impulses and transportation of materials within neurons, increase the risk of developing ALS. […] Gene mutations that are risk factors for ALS may add, delete, or change DNA building blocks (nucleotides), resulting in the production of a protein with an altered or reduced function.

• #2 Amyotrophic lateral sclerosis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-3

  20% of cases with autosomal dominant FALS and 2% of patients with SALS show mutations in the Copper-Zinc superoxide dismutase (SOD1) gene. Mutations in the gene are thought to cause disease through a toxic gain of function rather than causing impairment of the antioxidant function of the SOD1 enzyme. Other genes causing familial MND include alsin (ALS2), senataxin (ALS4), Vesicle associated membrane protein (VAPB, ALS8), Angiogenin and a mutation in the p150 subunit of dynactin (DCTN1). Recently, mutations in TARDBP gene (encoding the TAR-DNA binding protein TDP-43) located on chromosome 1p36.22 have been linked to familial and sporadic ALS. Several other gene mutations have been identified in sporadic cases which may increase susceptibility to ALS, such as mutations in the KSP repeat region in the NEFH gene (encoding neurofilament heavy subunit), apolipoprotein E 4 genotype (APOE), decreased expression of EAAT2 protein and alterations in the Vascular endothelial growth factor (VEGF) gene to name a few.

• #2 Amyotrophic Lateral Sclerosis (ALS): What It Is & Symptoms

  https://my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als

  Amyotrophic lateral sclerosis, or ALS, is a neurodegenerative disease that targets the nerve cells (neurons) in your brain and spinal cord. It affects your muscle control. Symptoms worsen over time. […] Researchers dont know what causes amyotrophic lateral sclerosis. They believe its a combination of the following factors: […] About 70% of familial cases and 5% to 10% of sporadic cases involve gene changes. Theyre most often in the C9orf72, SOD1, TARDBP and FUS genes. There are more than 40 related genes. […] Exposure to toxins (like lead or mercury), viruses or trauma may also play a role. […] Some types of amyotrophic lateral sclerosis are genetic. You can inherit genetic changes that cause ALS from your biological parents. Inherited ALS isnt common, though. Sometimes, genetic changes happen randomly, without a history in your biological family. […] Theres no proven way to prevent ALS. Research is ongoing to learn more about the causes and risk factors to help create prevention methods in the future.

• #2 ALS Pathophysiology – ALS Causes | ALS Pathways

  https://www.alspathways.com/hcp/rethinking-als/

  While our knowledge of the pathogenesis of ALS remains incomplete, new and exciting research continues to uncover information about the pathophysiology and underlying causes of ALS. […] Research suggests many factors may contribute to motor neuron cell deterioration, including: oxidative stress, defective glutamate metabolism, mitochondrial dysfunction, genetic variations, apoptosis, cytoskeletal protein defects preventing normal cell movement and division, autoimmune dysfunction, inflammatory responses.

• #2 Causes/Inheritance – Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/amyotrophic-lateral-sclerosis/causes-inheritance

  There is evidence that the immune system, particularly immune cells in the nervous system known as microglia, can be both beneficial and harmful in ALS. […] Glutamate carries signals between neurons (nerve cells), and there may be too much of it in ALS. […] For years, experts have tried to find factors common to people who develop ALS, such as environmental toxins, occupational hazards, places of work or residence, exposure to chemicals, and others. […] The term „familial” ALS means that there is more than one occurrence of the disease in a family. The term „sporadic” applies when there is no known history of other family members with the disease. […] SOD1 and C9orf72 are the most common genetic causes for ALS. […] Mutations in the SOD1 gene account for about 15% of familial ALS within European populations, 30% among Asian populations, and some cases of sporadic ALS.

• #2 An Overview of Causes and Risk Factors for ALS

  https://www.neurologylive.com/view/an-overview-of-causes-and-risk-factors-for-als

  This is a hard question to answer because we do not know. For about 1 in every 10 patients, there is clearly a family history. […] The first gene that was clearly shown to be responsible for some forms of inherited ALS was discovered in 1992: a gene for superoxide dismutase [SOD]. […] The largest contributor to inherited ALS is a gene that was discovered more recently called C9orf72. This is also primarily autosomal dominant. It is probably responsible for about 50% of inherited ALS. […] A defect can occur in what we call protein misfolding. […] We know that inflammation plays a role in ALS in various forms of inflammatory cells, specifically microglia and T-regulatory cells, may be dysfunctional or may promote damage in ALS. […] The first thing to say is that we already know some of those same genes that cause familial ALS also apparently cause sporadic ALS.

• #2 How is ALS Diagnosed and Treated? | ALS Program at HSS

  https://www.hss.edu/condition-list_amyotrophic-lateral-sclerosis.asp

  Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease or motor neuron disease, is a progressive, degenerative disease that destroys the nerve cells that control voluntary muscle movement. […] Although the cause of ALS is not completely understood, recent research suggests that multiple complex factors contribute to the death of motor neurons. Specific risk factors for ALS have not been conclusively identified, but ongoing research is exploring the possible role of genetics and/or environmental factors. Research published in 2009 suggests that smoking tobacco may heighten a person’s risk for ALS. […] Any one or more of the following factors may be responsible for the disease: defective glutamate metabolism, free radical injury, mitochondrial dysfunction, gene defects, programmed cell death or apoptosis, cytoskeletal protein defects, autoimmune and inflammatory mechanisms, accumulation of protein aggregates (clumps), viral infections. […] It is also likely that specific gene mutations and/or inherited traits modify the disease and increase one’s likelihood of developing it.

• #2 Amyotrophic Lateral Sclerosis (ALS): Facts & Symptoms of Lou Gehrig’s Disease | Live Science

  https://www.livescience.com/39583-als-lou-gehrigs-disease.html

  Scientists have identified more than a dozen other genetic mutations that may be linked to ALS. These mutations cause changes in the processing of RNA molecules (which may regulate genes), defects in the recycling of proteins, defects in motor neuron shape and structure, or susceptibility to environmental toxins. […] Other research suggests ALS may share similarities to frontotemporal dementia (FTD), a degenerative disease of the brain’s frontal lobe. A defect in the C9orf72 gene is found in a substantial number of ALS patients as well as some FTD patients. […] A 2017 paper by R. L. McLaughlin, et al, suggests that there might be also be a genetic relationship between ALS and schizophrenia. The affected gene is the same as the gene found to have a defect in the FTD study.

• #2 Amyotrophic Lateral Sclerosis: Lou Gehrig’s Disease | AAFP

  https://www.aafp.org/pubs/afp/issues/1999/0315/p1489.html

  Other hypothetic causes of ALS include neurotoxicity from various metals, chemicals or foods, and, conversely, deficiency of neurotrophic agents (poorly understood proteins that enhance neuronal maintenance and growth). […] An intriguing theory that brings together several factors holds that ALS develops when vulnerable persons are exposed to a neurotoxin at times of strenuous physical activity. […] The mechanisms responsible for ALS operate long before the onset of symptoms. An estimated one third of motor neurons must be destroyed before muscle atrophy becomes apparent.

• #2 About Amyotrophic Lateral Sclerosis (ALS) | National ALS Registry | CDC

  https://www.cdc.gov/als/abouttheregistrymain/about-amyotrophic-lateral-sclerosis-als.html

  No one knows what causes most cases of ALS. […] No cause has been found for most cases of ALS. In the future, scientists may find that many factors together cause ALS. […] Health studies have not found definite environmental factors that are linked with either ALS or other MNDs. […] Some studies suggested a possible link with exposure to heavy metals (e.g., lead and mercury). […] Other studies suggested a link with exposure to trace elements, solvents, radiation, and agricultural chemicals. […] About 510% of ALS cases occur within families. This is called familial ALS and it means that two or more people in a family have ALS. These cases are caused by several inherited factors. The most common is in a gene called SOD1. […] Familial ALS is found equally among men and women.

• #2 Risk factors for amyotrophic lateral sclerosis | CLEP

  https://www.dovepress.com/risk-factors-for-amyotrophic-lateral-sclerosis-peer-reviewed-fulltext-article-CLEP

  According to an evidence-based medicine analysis, smoking is the only probable risk factor for ALS. […] The most investigated relationship between dietary factors and ALS is the inverse association between higher intake of antioxidants and a lower risk of ALS. […] There is a strong clinical impression that ALS patients have a higher level of physical fitness and lower body mass index (BMI) than average. […] Workers in various occupations with seemingly disparate exposures have been reported to be potentially at altered risk of ALS, including athletes, carpenters, cockpit workers, construction workers, electrical workers, farm workers, hairdressers, house painters, laboratory technicians, leather workers, machine assemblers, medical service workers, military workers, nurses, power production plant workers, precision metal workers, programmers, rubber workers, shepherds, tobacco workers, veterinarians, and welders.

• #2 Amyotrophic Lateral Sclerosis: Disease State Overview

  https://www.ajmc.com/view/amyotrophic-lateral-sclerosis-disease-state-overview

  Amyotrophic lateral sclerosis (ALS) is a disease that results in the progressive deterioration and loss of function of the motor neurons in the brain and spinal cord, leading to paralysis. […] Due to the collection of information from the participation of patients with ALS in registries, biomarkers and genes associated with ALS have been discovered. […] Potential risk factors for the development of ALS include family history, occupations associated with heavy manual labor, agricultural work, military service (particularly in the Gulf War), football, pesticides, chemicals, smoking, heavy metals, geography, and electric shock. […] Studies suggest an association with ALS and the following: cyanotoxins, football, geography, smoking, heavy metals, electric shock, pesticides and chemicals, and military service, but there is no clear evidence to prove causation.

• #2 Amyotrophic lateral sclerosis (ALS) Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/amyotrophic-lateral-sclerosis-als

  Amyotrophic lateral sclerosis, or ALS, is a disease of the nerve cells in the brain, brain stem and spinal cord that control voluntary muscle movement. […] One in 10 cases of ALS is due to a genetic variant. The cause is unknown in most other cases. […] Having a family member who has a hereditary form of the disease is a risk factor for ALS. Other risks include military service. The reasons for this are unclear, but it may have to do with environmental exposure to toxins.

• #2 The mystery of why some people develop ALS

  https://www.bbc.com/future/article/20230825-the-mystery-of-why-some-people-develop-als

  Changes in up to 40 genes have been implicated in increasing someone’s risk for sporadic ALS, though the condition is extremely rare. […] However, there’s also emerging evidence that repeated and prolonged exposure to potential triggers in the external environment might increase the risk of someone developing ALS, particularly the sporadic form. […] Neil Thakur, chief mission officer of the ALS Association, says there is not a complete cause and effect for ALS. „It is always a combination of factors,” he says. […] But there is some evidence that exposure to particulates from diesel fuel, aviation fuel, particulates from burn pits, pesticides and aerosols may increase someone’s risk of developing ALS, he adds. […] There’s also evidence that having lead in your drinking water, smoking and contact sports might trigger ALS.

• #2 Amyotrophic Lateral Sclerosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556151/

  Over 120 genes have been implicated in ALS. […] A prevailing thought is that the accumulation of abnormal proteins due to aberrant RNA processing is involved in the development of ALS. […] The risk variables include sports with a high incidence of concussions, military jobs, smoking, exposure to heavy metals (lead, manganese), pesticides, neurotoxins (cyanobacteria), and electromagnetic fields.

• #2 Who Gets ALS?

  https://www.webmd.com/brain/who-gets-als

  Mutations on this gene appear in about 20% of familial cases and 1% to 5% of sporadic ones. Its unclear how the mutations lead to ALS. […] Scientists are also looking at whether things in the environment such as chemicals and other agents can raise your chances of getting ALS. […] Smoking is believed to be the only probable factor that may raise your chances for ALS. […] Lead and other chemicals may be linked to ALS, but no single agent has been consistently found to be a cause. […] Studies have found that military veterans, especially those deployed during the Gulf War in 1991, have a greater chance of ALS. […] The most famous person to have ALS was Lou Gehrig, the baseball player who died from it. […] Several lines of work — including sports, cockpit, construction, farm, hairdressing, lab, veterinary, and welding, among many others — have been reported to carry a higher chance of ALS. […] Clusters of ALS cases have been reported on the Pacific island of Guam and in the Kii Peninsula in Japan, which have rates 50 to 100 times higher than other parts of the world.

• #2 Amyotrophic lateral sclerosis (ALS) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022

  ALS is often called Lou Gehrig’s disease after the baseball player who was diagnosed with it. The exact cause of the disease is still not known. A small number of cases are inherited. […] For about 10% of people with ALS, a genetic cause can be identified. For the rest, the cause is not known. […] Researchers continue to study possible causes of ALS. Most theories center on a complex interaction between genes and factors in the environment. […] ALS causes both groups of motor neurons to gradually deteriorate and then die. When motor neurons are damaged, they stop sending messages to the muscles. As a result, the muscles can’t function.

• #2 The mystery of why some people develop ALS

  https://www.bbc.com/future/article/20230825-the-mystery-of-why-some-people-develop-als

  Scientists are racing to find out what causes this progressive disease. And they’re starting to make some headway. […] The reasons why people develop ALS are complicated. For 10-15% of people with the condition, it runs in the family. In these cases, a mutation in a particular gene would have been passed through the generations. […] However, it turns out that when people do develop the inherited form of ALS, the affected gene is not always the same one, even though the consequences are the same. […] For the other 85% of people who develop ALS, identifying the cause is even less straightforward. […] Recent research has suggested that genetic mutations might be part of the story. However, these probably involve little changes in a few different genes rather the single drastic, obvious biological mistakes noted for familial ALS.

• #2 The mystery of why some people develop ALS

  https://www.bbc.com/future/article/20230825-the-mystery-of-why-some-people-develop-als

  Feldman also says that her team’s research looking at the combined risk from genetic and environmental factors „is a challenge” because they suspect that multiple genes tens and possibly even hundreds contribute to what they term the „polygenic risk profile” in ALS. […] The challenge, however, is funding for appropriate research. As well as working out how much of a contribution each gene or environmental factor might make, more studies are needed on how to apply any knowledge gained.

• #2 Amyotrophic Lateral Sclerosis (ALS): Causes and Symptoms

  https://www.aarp.org/health/conditions-treatments/info-2024/amyotrophic-lateral-sclerosis-als.html

  The vast majority of people with ALS 9 in 10 did not inherit a gene from a family member and have no family history of the disease. […] Aside from these known risk factors, smokers may be more likely to develop ALS, as are people whove been exposed to environmental toxins, such as lead or certain chemicals, research suggests. […] For some reason, perhaps due to toxic exposures, people who have served in the military seem to be at higher risk. […] There are around 40 known genes that cause genetic ALS. […] The important thing is that they were able to develop a therapy that went straight for that gene and repaired it, Dave says. […] Hes optimistic that the same approach can be used to mute the effects of other genes gone awry in ALS: Now we have the formula to do this for the other 39 genes. […] Researchers are getting closer to understanding how to use this protein as a blood biomarker for the disease in all patients.

• #2

  https://www.feinberg.northwestern.edu/research/podcast/what-causes-als-with-robert-kalb-md.html

  We think that a major problem in ALS is the recognition of damaged proteins and disposal of them. […] If you could facilitate the recognition and degradation of a protein and that recognition process could be drugged, if we could make a drug that would accelerate that process, we think that that’s gonna be an opportunity for treating patients.

• #2 An Overview of Causes and Risk Factors for ALS

  https://www.neurologylive.com/view/an-overview-of-causes-and-risk-factors-for-als

  Finding environmental risk factors is much trickier because, although the genome is vast, it is a finite thing, and we know what we are testing. […] To make a point on that, Jinsy mentioned that military service during times of conflict is fairly clearly a risk factor for ALS, in the United States at least. […] Another factor to consider is that, for something we think might be a risk factor, the way we interpret it can be biased.

• #2 Amyotrophic Lateral Sclerosis (ALS) | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als

  Other studies are working to identify additional genes that may cause or put a person at risk for either familial or sporadic ALS. […] A large-scale collaborative research effort supported by NINDS, other NIH institutes, and several public and private organizations is analyzing genetic data from thousands of individuals with ALS to discover new genes involved in the disease. […] Additionally, researchers are looking at the potential role of epigenetics in ALS development. […] NINDS supports research on the development of biomarkersbiological measures of a disease. […] ALS biomarkers can help identify the rate of progression and the effectiveness of current and future therapies.

• #2 ALS – Wikipedia

  https://en.wikipedia.org/wiki/ALS

  Most cases of ALS (about 90-95%) have no known cause, and are known as sporadic ALS. […] However, both genetic and environmental factors are believed to be involved. […] The remaining 5-10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). […] It is not known what causes sporadic ALS, hence it is described as an idiopathic disease. […] Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. […] The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. […] A multi-step liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. […] The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. lead and mercury), chemicals (e.g. pesticides and solvents), electric shock, physical injury (including head injury), and smoking (in men more than women).

• #2

  https://www.feinberg.northwestern.edu/research/podcast/what-causes-als-with-robert-kalb-md.html

  The good news is that we’ve learned much more about the disease over the past decades. […] The key here is to understand the underlying basic biology that’s going wrong in motor neurons and cells that are supporting them and intervene. […] I’m quite sure that at some point there will be a pill, you take the pill in the morning, once a day, and the disease never progresses. […] There’s a childhood disease called spinal muscular atrophy. It’s a childhood motor neuron disease. Over the past 20 years we’ve identified with a genetic abnormality is in spinal muscular atrophy. […] Most individuals who have ALS have a sporadic form of disease, which means that there’s no clear genetic cause and about 10 or 15 percent, there’s a clear single gene which is mutated that causes the disease and you can track it through a family.

• #3 ALS – Wikipedia

  https://en.wikipedia.org/wiki/ALS

  Most cases of ALS (about 90-95%) have no known cause, and are known as sporadic ALS. […] However, both genetic and environmental factors are believed to be involved. […] The remaining 5-10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). […] It is not known what causes sporadic ALS, hence it is described as an idiopathic disease. […] Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. […] The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. […] A multi-step liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. […] The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. lead and mercury), chemicals (e.g. pesticides and solvents), electric shock, physical injury (including head injury), and smoking (in men more than women).

• #3 Amyotrophic Lateral Sclerosis (ALS) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/amyotrophic-lateral-sclerosis

  ALS is characterized by the gradual degeneration and death of motor neurons, which are the nerve cells in the brain and spinal cord that control voluntary muscles, such as those involved in walking and talking. […] The exact cause of ALS is unknown. However, it is believed that a combination of genetic and environmental factors contributes to the development of the disease. […] In 90% of cases, ALS is sporadic, meaning it occurs without known risk factors or a family history of the condition. […] In about 10%-15% of cases, ALS is familial. Roughly 70% of familial ALS and 15% of sporadic ALS have mutations in known ALS genes, including SOD1, FUS, TARDBP, C9ORF72, and ATXN2, among others. It is important to note that presence of certain gene mutations doesn’t necessarily mean that someone will develop ALS. […] Although the exact cause of ALS is not known, certain factors may increase a person’s risk. These include age, male sex, genetic risk factors, lifestyle risk factors, occupational risk factors, and environmental risk factors.

• #3 An Overview of Causes and Risk Factors for ALS

  https://www.neurologylive.com/view/an-overview-of-causes-and-risk-factors-for-als

  This is a hard question to answer because we do not know. For about 1 in every 10 patients, there is clearly a family history. […] The first gene that was clearly shown to be responsible for some forms of inherited ALS was discovered in 1992: a gene for superoxide dismutase [SOD]. […] The largest contributor to inherited ALS is a gene that was discovered more recently called C9orf72. This is also primarily autosomal dominant. It is probably responsible for about 50% of inherited ALS. […] A defect can occur in what we call protein misfolding. […] We know that inflammation plays a role in ALS in various forms of inflammatory cells, specifically microglia and T-regulatory cells, may be dysfunctional or may promote damage in ALS. […] The first thing to say is that we already know some of those same genes that cause familial ALS also apparently cause sporadic ALS.

• #4 Amyotrophic Lateral Sclerosis (ALS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/amyotrophic-lateral-sclerosis

  The causes of the vast majority of ALS cases are still unknown. Investigators theorize that some individuals may be genetically predisposed to developing the disease but do so only after coming into contact with an environmental trigger. The interaction of genetics and environment may hold clues as to why some individuals develop ALS. […] Although the majority of ALS cases are sporadic, meaning there is no family history of the disease, about 10% of cases are familial, meaning the disease runs in the family. A common misconception is that only familial ALS is „genetic.” Actually, both familial and sporadic ALS can stem from genetic causes, and some people who have a diagnosis of sporadic ALS may carry ALS-causing genetic mutations that can be passed on to offspring. A genetic counselor can help people with ALS understand inheritance and any associated risks for family members.

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