Polyglutamine neurodegeneration: protein misfolding revisited.
Polyglutamine diseases are a major cause of neurodegeneration worldwide. Recent studies highlight the importance of protein quality control mechanisms in regulating polyglutamine-induced toxicity. Here we discuss a model of disease pathogenesis that integrates current understanding of the role of protein folding in polyglutamine disease with emerging evidence that alterations in native protein interactions contribute to toxicity. We also incorporate new findings on other age-related neurodegenerative diseases in an effort to explain how protein aggregation and normal aging processes might be involved in polyglutamine disease pathogenesis.
Williams
Aislinn J
AJ
Program in Neuroscience and Medical Scientist Training Program, University of Iowa, 2206 MERF, Iowa City, IA 52242, USA.
Paulson
Henry L
HL
D000375:Aging / Q000502:physiology; D000818:Animals; D006801:Humans; D008954:Models, Biological; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D017510:Protein Folding
D010455:Peptides; C097188:polyglutamine
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