Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review highlights recent epidemiologic, clinical-genetic, and neurochemical advances in our understanding of sporadic amyotrophic lateral sclerosis (ALS) and their relationships to familial ALS caused by superoxide dismutase (SOD1) gene mutations. It is of fundamental importance to recognize that ALS is a biologically heterogeneous syndrome in which genetics, environment, and aging are inter-related. The discovery of mutations in the SOD1 gene is the greatest breakthrough in ALS research since Charcot's description of the disorder, but the putative toxic gain of function of mutant SOD1 remains elusive despite intense research. Currently, two dominant theories for the pathogenesis of SOD1 mutations exist: specific protein cytotoxicity and protein aggregation. Mutant SOD1 interacts specifically with neurofilament-light chain mRNA and the dynein/dynactin complex, suggesting that cytoskeletal defects and axonal transport are key players. In addition, mutant SOD1 protein has increased propensity to form aggregate-prone monomers, and the degree of instability correlates inversely with length of survival; therefore, increased propensity to aggregate may be the unifying common denominator for the 119 diverse SOD1 mutations.
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PMID:Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. 1646 70

Neurofilaments are elevated in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients. However, timing of this increase is unknown. To characterize the premanifest disease phase, we performed a cross-sectional study on asymptomatic (n = 12) and symptomatic (n = 64) ALS mutation carriers and family controls (n = 19). Neurofilaments NF-L (neurofilament-light chain) and pNF-H (phosphorylated neurofilament-heavy chain) are normal before symptom onset and increased by at least an order of magnitude at early symptom onset in CSF (pNF-H) or serum and CSF (NF-L). Thus, blood and CSF neurofilament levels are linked to the symptomatic phase of ALS and might serve as objective markers of structural damage to the nervous system.
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PMID:Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. 2652 63