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 article

    85 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

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology

    Fingerprint Dive into the research topics of 'Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease'. Together they form a unique fingerprint.

  • Cite this