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

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2010

Autores

Jorge M A Oliveira (Autor) FFUP

Revista

Título: Journal of Neurochemistry

Vol. 114 Nº 1

Páginas: 1-12

ISSN: 0022-3042

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 93 Citações

Scopus - 112 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12