Increased mitochondrial fission and neuronal dysfunction in Huntington's disease

Implications for molecular inhibitors of excessive mitochondrial fission

P (Hemachandra) Reddy

    Research output: Contribution to journalArticle

    43 Citations (Scopus)

    Abstract

    Huntington's disease (HD) is a fatal, progressive neurodegenerative disease with an autosomal dominant inheritance, characterized by chorea, involuntary movements of the limbs and cognitive impairments. Since identification of the HD gene in 1993, tremendous progress has been made in identifying underlying mechanisms involved in HD pathogenesis and progression, and in developing and testing molecular therapeutic targets, using cell and animal models of HD. Recent studies have found that mutant Huntingtin (mHtt) interacts with Dynamin-related protein 1 (Drp1), causing excessive fragmentation of mitochondria, leading to abnormal mitochondrial dynamics and neuronal damage in HD-affected neurons. Some progress has been made in developing molecules that can reduce excessive mitochondrial fission while maintaining both the normal balance between mitochondrial fusion and fission, and normal mitochondrial function in diseases in which excessive mitochondrial fission has been implicated. In this article, we highlight investigations that are determining the involvement of excessive mitochondrial fission in HD pathogenesis, and that are developing inhibitors of excessive mitochondrial fission for potential therapeutic applications.

    Original languageEnglish (US)
    Pages (from-to)951-955
    Number of pages5
    JournalDrug Discovery Today
    Volume19
    Issue number7
    DOIs
    StatePublished - 2014

    Fingerprint

    Mitochondrial Dynamics
    Huntington Disease
    Dynamins
    Chorea
    Dyskinesias
    Neurodegenerative Diseases
    Disease Progression
    Mitochondria
    Extremities
    Animal Models
    Neurons
    Therapeutics
    Genes

    ASJC Scopus subject areas

    • Drug Discovery
    • Pharmacology

    Cite this

    Increased mitochondrial fission and neuronal dysfunction in Huntington's disease : Implications for molecular inhibitors of excessive mitochondrial fission. / Reddy, P (Hemachandra).

    In: Drug Discovery Today, Vol. 19, No. 7, 2014, p. 951-955.

    Research output: Contribution to journalArticle

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