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Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis.


ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron degenerative disease whose etiology and pathogenesis remain poorly understood. Most cases of ALS ( approximately 90%) are sporadic (SALS), occurring in the absence of genetic associations. Approximately 20% of familial ALS (FALS) cases are due to known mutations in the copper, zinc superoxide dismutase (SOD1) gene. Molecular evidence for a common pathogenesis of SALS and FALS has remained elusive. Here we use covalent chemical modification to reveal an attribute of spinal cord SOD1 common to both SOD1-linked FALS and SALS, but not present in normal or disease-affected tissues from other neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases and spinal muscular atrophy, a non-ALS motor neuron disease. Biotinylation reveals a 32-kDa, covalently cross-linked SOD1-containing protein species produced not only in FALS caused by SOD1 mutation, but also in SALS. These studies use chemical modification as a novel tool for the detection of a disease-associated biomarker. Our results identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between SALS and FALS.

SUBMITTER: Gruzman A 

PROVIDER: S-EPMC1941502 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis.

Gruzman Arie A   Wood William L WL   Alpert Evgenia E   Prasad M Dharma MD   Miller Robert G RG   Rothstein Jeffery D JD   Bowser Robert R   Hamilton Ronald R   Wood Troy D TD   Cleveland Don W DW   Lingappa Vishwanath R VR   Liu Jian J  

Proceedings of the National Academy of Sciences of the United States of America 20070716 30


Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron degenerative disease whose etiology and pathogenesis remain poorly understood. Most cases of ALS ( approximately 90%) are sporadic (SALS), occurring in the absence of genetic associations. Approximately 20% of familial ALS (FALS) cases are due to known mutations in the copper, zinc superoxide dismutase (SOD1) gene. Molecular evidence for a common pathogenesis of SALS and FALS has remained elusive. Here we use covalent chemical mod  ...[more]

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