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Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective

P Hemachandra Reddy1, Ulziibat P Shirendeb

  • 1Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. reddyh@ohsu.edu

Biochimica Et Biophysica Acta
|November 15, 2011
PubMed

Insights

Huntington's disease involves mutant huntingtin protein disrupting mitochondrial function, causing neuronal damage. Therapies targeting mitochondrial fragmentation may offer new treatment avenues for this progressive neurodegenerative disorder.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Huntington's disease (HD) is a fatal neurodegenerative disorder.
  • It is caused by expanded polyglutamine repeats in the HD gene.
  • HD symptoms include motor, cognitive, and emotional disturbances.

Purpose of the Study:

  • To summarize recent advancements in Huntington's disease research.
  • To focus on the role of mitochondrial dynamics and axonal transport defects in HD neurons.
  • To discuss therapeutic strategies for reducing mitochondrial fragmentation and neuronal damage in HD.

Main Methods:

  • Review of current research on mutant huntingtin (Htt) and mitochondria.
  • Analysis of the interaction between mutant Htt and dynamin-related protein 1 (Drp1).
  • Investigation of mitochondrial fragmentation and axonal transport in HD models.

Main Results:

  • Mutant Htt interacts with Drp1, enhancing its activity.
  • This interaction leads to excessive mitochondrial fragmentation and abnormal distribution.
  • Defective axonal transport of mitochondria and synaptic degeneration are observed.

Conclusions:

  • Abnormal mitochondrial dynamics and axonal transport are key features of HD neurons.
  • Therapeutic strategies aimed at decreasing mitochondrial fragmentation show promise for HD treatment.

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