ALS-associated peripherin spliced transcripts form distinct protein inclusions that are neuroprotective against oxidative stress

Intracellular proteinaceous inclusions are well-documented hallmarks of the fatal motor neuron disorder amyotrophic lateral sclerosis (ALS). The pathological significance of these inclusions remains unknown. Peripherin, a type III intermediate filament protein, is upregulated in ALS and identified a...

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Bibliographic Details
Published in:Experimental neurology 2014-11, Vol.261, p.217-229
Main Authors: McLean, Jesse R., Smith, Gaynor A., Rocha, Emily M., Osborn, Teresia M., Dib, Samar, Hayes, Melissa A., Beagan, Jonathan A., Brown, Tana B., Lawson, Tristan F.S., Hallett, Penelope J., Robertson, Janice, Isacson, Ole
Format: Article
Language:English
Subjects:
Aggregation
Amyotrophic lateral sclerosis (ALS)
Carcinoma - pathology
Cell Line, Tumor
DNA-Binding Proteins - metabolism
Dose-Response Relationship, Drug
Humans
Hydrogen Peroxide - pharmacology
Inclusion
Inclusion Bodies - genetics
Inclusion Bodies - metabolism
Intermediate filament
Oxidative Stress - drug effects
Oxidative Stress - genetics
Peripherin
Peripherins - genetics
Peripherins - metabolism
Protein Aggregation, Pathological - genetics
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proto-Oncogene Proteins c-myc - metabolism
RNA, Messenger - metabolism
Splicing
Stress
TDP-43
Time Factors
Transfection
Ubiquitin - metabolism
Vimentin - metabolism
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Summary:Intracellular proteinaceous inclusions are well-documented hallmarks of the fatal motor neuron disorder amyotrophic lateral sclerosis (ALS). The pathological significance of these inclusions remains unknown. Peripherin, a type III intermediate filament protein, is upregulated in ALS and identified as a component within different types of ALS inclusions. The formation of these inclusions may be associated with abnormal peripherin splicing, whereby an increase in mRNA retaining introns 3 and 4 (Per-3,4) leads to the generation of an aggregation-prone isoform, Per-28. During the course of evaluating peripherin filament assembly in SW-13 cells, we identified that expression of both Per-3,4 and Per-28 transcripts formed inclusions with categorically distinct morphology: Per-3,4 was associated with cytoplasmic condensed/bundled filaments, small inclusions (
ISSN:0014-4886
1090-2430
DOI:10.1016/j.expneurol.2014.05.024