Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2014 Oct 23

PMID 25336039

Citations 26

Authors

Guylaine Hoffner

Philippe Djian

Affiliations

Soon will be listed here.

Abstract

Huntington disease is a dominantly inherited disease of the central nervous system. The mutational expansion of polyglutamine beyond a critical length produces a toxic gain of function in huntingtin and results in neuronal death. In the course of the disease, expanded huntingtin is proteolyzed, becomes abnormally folded, and accumulates in oligomers, fibrils, and microscopic inclusions. The aggregated forms of the expanded protein are structurally diverse. Structural heterogeneity may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective. When defined, the toxic structures could then specifically be targeted by prophylactic or therapeutic drugs aimed at inhibiting polyglutamine aggregation.

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