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Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R115-23.

Polyglutamine diseases: emerging concepts in pathogenesis and therapy.

Author information

1
Department of Neurology, UCSF, San Francisco, CA 94143, USA.

Abstract

Polyglutamine diseases are a family of neurodegenerative conditions that each derive from a CAG triplet repeat expansion in a specific gene. This produces a pathogenic protein that contains a critically expanded tract of glutamines. These prototypical protein misfolding disorders include Huntington disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias. This article reviews the emerging concepts in pathogenesis and therapy. Key ideas include the role of proteolytic cleavage, the importance of conformational change in the pathogenic proteins, the role of protein aggregation and the importance of transcriptional and metabolic disturbances. The relative role of functional perturbation in a target protein induced by a polyglutamine expansion is also discussed. Therapeutic strategies include counteracting cellular perturbations and direct targeting of polyglutamine protein expression, cleavage or conformation.

PMID:
17911155
DOI:
10.1093/hmg/ddm213
[Indexed for MEDLINE]

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