Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment.

A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure.

Poirier MA, Jiang H, Ross CA

Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. mpoirie1@jhmi.edu

Huntington's disease (HD) arises from an expanded polyglutamine (polyQ) in the N-terminus of the huntingtin (htt) protein. Neuronal degeneration and inclusions containing N-terminal fragments of mutant htt are present in the cortex and striatum of HD brain. Recently, a model of polyQ aggregate structure has been proposed on the basis of studies with synthetic polyQ peptides and includes an alternating beta-strand/beta-turn structure with seven glutamine residues per beta-strand. We tested this model in the context of the htt exon-1 N-terminal fragment in both mammalian cell culture and cultured primary cortical neurons. We found our data support this model in the htt protein and provide a better understanding of the structural basis of polyQ aggregation in toxicity in HD.

Published 4 March 2005 in Hum Mol Genet, 14(6): 765-74.
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