Citation

Bano D, Zanetti F, Mende Y, Nicotera P. Cell Death Dis 2011; 2(online): e228.

Affiliation

Deutsches Zentrum für Neurodegenerative Erkrankungen, Bonn, Germany.

Copyright

(Copyright © 2011, Nature Publishing Group)

DOI

10.1038/cddis.2011.112

PMID

22071633

PMCID

PMC3223696

Abstract

Huntington's disease (HD) is a complex and severe disorder characterized by the gradual and the progressive loss of neurons, predominantly in the striatum, which leads to the typical motor and cognitive impairments associated with this pathology. HD is caused by a highly polymorphic CAG trinucleotide repeat expansion in the exon-1 of the gene encoding for huntingtin protein. Since the first discovery of the huntingtin gene, investigations with a consistent number of in-vitro and in-vivo models have provided insights into the toxic events related to the expression of the mutant protein. In this review, we will summarize the progress made in characterizing the signaling pathways that contribute to neuronal degeneration in HD. We will highlight the age-dependent loss of proteostasis that is primarily responsible for the formation of aggregates observed in HD patients. The most promising molecular targets for the development of pharmacological interventions will also be discussed.

Language: en