Nature and cause of mitochondrial dysfunction in Huntington's disease: focusing on huntingtin and the striatum

• Type: Another Publication in an International Scientific Journal
• Date: 2010

Authors

Jorge M A Oliveira (Author) FFUP

Journal

Title: Journal of Neurochemistry

Vol. 114 No. 1

Pages: 1-12

ISSN: 0022-3042

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 93 Citations

Scopus - 112 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-5BJ

DOI: 10.1111/j.1471-4159.2010.06741.x

Abstract (EN): P>Polyglutamine expansion mutation in huntingtin causes Huntington's disease (HD). How mutant huntingtin (mHtt) preferentially kills striatal neurons remains unknown. The link between mitochondrial dysfunction and HD pathogenesis stemmed from postmortem brain data and mitochondrial toxin models. Current evidence from genetic models, containing mHtt, supports mitochondrial dysfunction with yet uncertain nature and cause. Because mitochondria composition and function varies across tissues and cell-types, mitochondrial dysfunction in HD vulnerable striatal neurons may have distinctive features. This review focuses on mHtt and the striatum, integrating experimental evidence from patients, mice, primary cultures and striatal cell-lines. I address the nature (specific deficits) and cause (mechanisms linked to mHtt) of HD mitochondrial dysfunction, considering limitations of isolated vs. in situ mitochondria approaches, and the complications introduced by glia and glycolysis in brain and cell-culture studies. Current evidence relegates respiratory chain impairment to a late secondary event. Upstream events include defective mitochondrial calcium handling, ATP production and trafficking. Also, transcription abnormalities affecting mitochondria composition, reduced mitochondria trafficking to synapses, and direct interference with mitochondrial structures enriched in striatal neurons, are possible mechanisms by which mHtt amplifies striatal vulnerability. Insights from common neurodegenerative disorders with selective vulnerability and mitochondrial dysfunction (Alzheimer's and Parkinson's diseases) are also addressed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12