Mitochondrial structural and functional dynamics in Huntington's disease

P. Hemachandra Reddy, Peizhong Mao, Maria Manczak

Research output: Contribution to journalReview articlepeer-review

123 Scopus citations

Abstract

Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder, characterized by chorea, involuntary movements, and cognitive impairments. Tremendous progress has been made since the discovery of HD gene in 1993, in terms of developing animal models to study the disease process, unraveling the expression and function of wild-type and mutant huntingtin (Htt) proteins in the central and peripheral nervous systems, and understanding expanded CAG repeat containing mutant Htt protein interactions with CNS proteins in the disease process. HD progression has been found to involve several pathomechanisms, including expanded CAG repeat protein interaction with other CNS proteins, transcriptional dysregulation, calcium dyshomeostasis, abnormal vesicle trafficking, and defective mitochondrial bioenergetics. Recent studies have found that mutant Htt is associated with mitochondria and causes mitochondrial structural changes, decreases mitochondrial trafficking, and impairs mitochondrial dynamics in the neurons affected by HD. This article discusses recent developments in HD research, with a particular focus on intracellular and intramitochondrial calcium influx, mitochondrial DNA defects, and mitochondrial structural and functional abnormalities in HD development and progression. Further, this article outlines the current status of mitochondrial therapeutics with a special reference to Dimebon.

Original languageEnglish (US)
Pages (from-to)33-48
Number of pages16
JournalBrain Research Reviews
Volume61
Issue number1
DOIs
StatePublished - Jun 2009
Externally publishedYes

Keywords

  • Calcium dyshomeostasis
  • Dimebon
  • Huntington's Disease
  • Mitochondria
  • Mitochondrial dynamics
  • Polyglutamine repeat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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