Lookup NU author(s): Dr Jorge Oliveira,
Professor Robert Lightowlers
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Polyglutamine expansions in huntingtin (Htt) are known to cause the profound neurodegenerative disorder, Huntington's disease (HD). Mitochondrial dysfunction has long been implicated in the pathophysiology of HD, but the underlying mechanism remains obscure. An article by Costa et al in this months edition describes a smooth mechanistic cascade from the well-accepted upstream event that mutant Htt is associated with Ca2+ handling abnormalities, through to apoptotic neuronal death. The proposed cascade implicates calcineurin, activated by abnormal Ca2+ levels, in the dephosphorylation of dynamin-1-like protein (Drp1.), increasing its association with mitochondria and promoting fission, cristae disruption, cytochrome c release and apoptosis (Fig 1). Together with the recent reports of increased mitochondrial fission in striatal neurons from HD patients, the article by Costa et al provides a compelling case for the role of abnormal mitochondrial networking in HD pathogenesis.
Author(s): Oliveira JMA, Lightowlers RN
Publication type: Article
Publication status: Published
Journal: EMBO Molecular Medicine
Print publication date: 29/11/2010
ISSN (print): 1757-4676
ISSN (electronic): 1757-4684
Publisher: Wiley-Blackwell Publishing Ltd.
Altmetrics provided by Altmetric