Is the mitochondrial outermembrane protein VDAC1 therapeutic target for Alzheimer's disease?

P (Hemachandra) Reddy

    Research output: Contribution to journalArticle

    46 Citations (Scopus)

    Abstract

    Mitochondrial dysfunction and synaptic damage have been described as early events in Alzheimer's disease (AD) pathogenesis. Recent research using AD postmortem brains, and AD mouse and cell models revealed that amyloid beta (Aβ) and tau hyperphosphorylation are involved in mitochondrial dysfunction and synaptic damage in AD. Further, recent research also revealed that the protein levels of mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1), are elevated in the affected regions of AD postmortem brains and cortical tissues from APP transgenic mice. In addition, emerging research using AD postmortem brains and AD mouse models revealed that VDAC1 is linked to Aβ and phosphorylated tau, blocks the mitochondrial permeability transition (MPT) pores, disrupts the transport of mitochondrial proteins and metabolites, impairs gating of VDAC, and causes defects in oxidative phosphorylation, leading to mitochondrial dysfunction in AD neurons. The purpose of this article is to review research that has investigated the relationship between VDAC1 and the regulation of MPT pores in AD progression.

    Original languageEnglish (US)
    Pages (from-to)67-75
    Number of pages9
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1832
    Issue number1
    DOIs
    StatePublished - Jan 2013

    Fingerprint

    Voltage-Dependent Anion Channel 1
    Mitochondrial Proteins
    Alzheimer Disease
    Therapeutics
    Brain Diseases
    Research
    Oxidative Phosphorylation
    Amyloid
    Transgenic Mice
    Disease Progression
    Carrier Proteins
    Membrane Proteins

    Keywords

    • Alzheimer's disease
    • Amyloid beta
    • Amyloid precursor protein
    • Mitochondrial dysfunction
    • Phoshorylated tau
    • Voltage-dependent anion channel

    ASJC Scopus subject areas

    • Molecular Biology
    • Molecular Medicine

    Cite this

    Is the mitochondrial outermembrane protein VDAC1 therapeutic target for Alzheimer's disease? / Reddy, P (Hemachandra).

    In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1832, No. 1, 01.2013, p. 67-75.

    Research output: Contribution to journalArticle

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