Amyotrophic Lateral Sclerosis (Als) is a significant neurodegenerative disorder affecting millions worldwide. This page provides comprehensive information about the disease, including its mechanisms, symptoms, diagnosis, and treatment approaches.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder characterized by the selective loss of upper and lower motor neurons in the brain and spinal cord. ALS leads to progressive muscle weakness, paralysis, and typically results in death within 2-5 years of symptom onset due to respiratory failure. The disease affects approximately 2-3 per 100,000 individuals annually, with a prevalence of about 10 per 100,000.
| Gene | Inheritance | Typical Onset | Notes |
|---|---|---|---|
| C9orf72 | Autosomal dominant | 40-60 years | Hexanucleotide repeat expansion; most common |
| SOD1 | Autosomal dominant | 40-60 years | First discovered ALS gene |
| FUS | Autosomal dominant | 40-50 years | RNA-binding protein |
| TARDBP | Autosomal dominant | 40-60 years | TDP-43 proteinopathy |
| ANG | Autosomal dominant | Variable | Angiogenin |
| TBK1 | Autosomal dominant | 40-70 years | Autophagy adapter |
Protein misfolding and aggregation
RNA metabolism dysfunction
Excitotoxicity
Mitochondrial dysfunction
Neuroinflammation
Axonal transport defects
| Stage | Symptoms | Timeline |
|---|---|---|
| Early | Focal weakness, fasciculations | 0-12 months |
| Middle | Widespread weakness, dysphagia | 12-36 months |
| Late | Respiratory failure, complete paralysis | 36-60 months |
| Drug | Mechanism | Effect |
|---|---|---|
| Riluzole | Anti-glutamatergic | ~3 month survival benefit |
| Tofersen | SOD1 ASO | Slows progression in SOD1ALS |
| Edaravone | Antioxidant | Modest functional benefit |
| Category | Biomarker | Utility |
|---|---|---|
| Neurofilament | NfL, pNfH | Disease progression, trial endpoint |
| Inflammation | CSF cytokines | Disease activity |
| Genetics | C9orf72, SOD1 | Diagnosis, clinical trials |
| Imaging | MRI, PET | Disease monitoring |
FUS Mutations in ALS - FUS gene mutations and their role in ALS pathogenesis
Proteins/TIA1 (TIA1L) - TIA1 stress granule protein linked to ALS
Proteins/PLA2G6 - Phospholipase involved in neurodegeneration
Proteins/FBXO7 - F-box protein linked to familial Parkinson's
Proteins/ATP13A2 - Lysosomal ATPase implicated in PD
Genes/GSTP1 - Glutathione S-transferase in oxidative stress
Proteins/PRKDC - DNA damage response kinase
Genes/CDNF - Cerebral dopamine neurotrophic factor
The study of Amyotrophic Lateral Sclerosis (Als) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
FUS Mutations in ALS - FUS gene mutations and their role in ALS pathogenesis