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 language | English (US) |
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Pages (from-to) | 251-255 |
Number of pages | 5 |
Journal | Current Opinion in Genetics and Development |
Volume | 22 |
Issue number | 3 |
DOIs | |
State | Published - 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 .