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Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by proteomic studies of animal models
Author(s) -
Jain Mohit Raja,
Ge Weiwen,
Elkabes Stella,
Li Hong
Publication year - 2008
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200780023
Subject(s) - amyotrophic lateral sclerosis , chaperone (clinical) , biology , proteome , proteomics , muscle atrophy , pathogenesis , genetically modified mouse , neurodegeneration , disease , superoxide dismutase , transgene , neuroscience , atrophy , bioinformatics , microbiology and biotechnology , pathology , oxidative stress , medicine , genetics , gene , immunology , biochemistry
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons and causes progressive muscle weakness and atrophy. The etiology and pathogenesis of ALS are largely unknown and no effective treatment is presently available. About 10% of patients have the familial or inherited form of the disease (fALS), among which 20% is linked to mutations with Cu 2+ /Zn 2+ superoxide dismutase ( mSOD1 ). Transgenic animals expressing human mSOD1 are excellent models for understanding not only fALS but sporadic ALS as well. Pathological features in both ALS patients and mSOD1 transgenic animals' spinal cords share commonalties including the accumulation of misfolded protein inclusions. Recent proteomic investigations on ALS animal models have discovered alterations in protein expression, protein‐protein interactions and post‐translational modifications. These efforts have revealed aspects of potential pathogenic mechanisms and identified probable therapeutic targets. The present review summarizes the major findings of proteomics studies performed on the mSOD1 mice with particular emphasis on the spinal cord proteome. These results are compared with those reported using cell cultures or specimens obtained from ALS patients. The convergence of pathogenic processes on protein chaperone function, and its relationship to protein degradation, metabolic dysfunction and oxidative signaling events is discussed.