Polyglutamine neurodegeneration: Expanded glutamines enhance native functions

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Abstract

An intriguing set of neurodegenerative disease are the nine disorders caused by the expansion of a unstable trinucleotide CAG repeat where the repeat is located within the coding of the affected gene, that is, the polyglutamine (polyQ) diseases. A gain-of-function mechanism for toxicity in polyQ diseases is widely thought to have a major role in pathogenesis. Yet, the specific nature of this gain-of-function is a matter of considerable discussion. The basic issue concerns whether toxicity stems from the native or normal function of the affected protein versus a novel function induced by polyQ expansion. For at least three of the polyQ disease considerable evidence is accumulating that pathology is mediated by a polyQ-induced exaggeration of a native function of the host protein.

Original languageEnglish (US)
Pages (from-to)251-255
Number of pages5
JournalCurrent Opinion in Genetics and Development
Volume22
Issue number3
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
I thank Jillian Frisch for her expert assistance in figure design. The research presented from the author's was supported by NIH/NINDS grants NS22920-23 and NS45667-09 .

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