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Distinct biochemical signatures characterize peripherin isoform expression in both traumatic neuronal injury and motor neuron disease
Author(s) -
McLean Jesse,
Liu HsuehNing,
Miletic Denise,
Weng Yuan Cheng,
Rogaeva Ekaterina,
Zinman Lorne,
Kriz Jasna,
Robertson Janice
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06846.x
Subject(s) - peripherin , gene isoform , amyotrophic lateral sclerosis , motor neuron , biology , intermediate filament , intermediate filament protein , microbiology and biotechnology , genetically modified mouse , neuroscience , transgene , pathology , disease , genetics , gene , medicine , cell , spinal cord , cytoskeleton
J. Neurochem. (2010) 114 , 1177–1192. Abstract Peripherin is a type III intermediate filament protein that is up‐regulated during neuronal injury and is a major component of pathological inclusions found within degenerating motor neurons of patients with amyotrophic lateral sclerosis (ALS). The relationship between these inclusions and their protein constituents remains largely unknown. We have previously shown that peripherin expression is characterized by tissue‐specific, intra‐isoform associations that contribute to filament structure; changes to the normal isoform expression pattern is associated with malformed filaments and intracellular inclusions. Here, we profile peripherin isoform expression and ratio changes in traumatic neuronal injury, transgenic mouse models of motor neuron disease, and ALS. Extensive western blot analyses of Triton X‐100 soluble and insoluble fractions of neuronal tissue from these conditions revealed significant changes in peripherin isoform content which could be differentiated by electrophoretic banding patterns to produce distinct peripherin biochemical signatures. Significantly, we found that the pattern of peripherin expression in ALS most closely approximates that of peripherin over‐expressing mice, but differs with regard to inter‐individual variations in isoform‐specific expression. Overall, these results provide important insights into complex post‐transcriptional processes that may underlie a continuum between peripherin‐mediated neuronal repair and its role in the pathogenesis of motor neuron disease.