Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease

P. Hemachandra Reddy, Ulziibat P. Shirendeb

Research output: Contribution to journalReview articlepeer-review

101 Scopus citations

Abstract

Huntington's disease (HD) is a progressive, fatal neurodegenerative disease caused by expanded polyglutamine repeats in the HD gene. HD is characterized by chorea, seizures, involuntary movements, dystonia, cognitive decline, intellectual impairment and emotional disturbances. Research into mutant huntingtin (Htt) and mitochondria has found that mutant Htt interacts with the mitochondrial protein dynamin-related protein 1 (Drp1), enhances GTPase Drp1 enzymatic activity, and causes excessive mitochondrial fragmentation and abnormal distribution, leading to defective axonal transport of mitochondria and selective synaptic degeneration. This article summarizes latest developments in HD research and focuses on the role of abnormal mitochondrial dynamics and defective axonal transport in HD neurons. This article also discusses the therapeutic strategies that decrease mitochondrial fragmentation and neuronal damage in HD.

Original languageEnglish (US)
Pages (from-to)101-110
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1822
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • Abnormal mitochondrial dynamics
  • BACHD mouse
  • Defective axonal transport
  • Mitochondrial trafficking
  • Mutant huntingtin
  • RNA silencing

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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