Dynamics of Dynamin-Related Protein 1 in Alzheimer's Disease and Other Neurodegenerative Diseases

Darryll Oliver, P. Hemachandra Reddy

    Research output: Contribution to journalReview articlepeer-review

    32 Scopus citations

    Abstract

    The purpose of this article is to highlight the role of dynamin-related protein 1 (Drp1) in abnormal mitochondrial dynamics, mitochondrial fragmentation, autophagy/mitophagy, and neuronal damage in Alzheimer's disease (AD) and other neurological diseases, including Parkinson's, Huntington's, amyotrophic lateral sclerosis, multiple sclerosis, diabetes, and obesity. Dynamin-related protein 1 is one of the evolutionarily highly conserved large family of GTPase proteins. Drp1 is critical for mitochondrial division, size, shape, and distribution throughout the neuron, from cell body to axons, dendrites, and nerve terminals. Several decades of intense research from several groups revealed that Drp1 is enriched at neuronal terminals and involved in synapse formation and synaptic sprouting. Different phosphorylated forms of Drp1 acts as both increased fragmentation and/or increased fusion of mitochondria. Increased levels of Drp1 were found in diseased states and caused excessive fragmentation of mitochondria, leading to mitochondrial dysfunction and neuronal damage. In the last two decades, several Drp1 inhibitors have been developed, including Mdivi-1, Dynasore, P110, and DDQ and their beneficial effects tested using cell cultures and mouse models of neurodegenerative diseases. Recent research using genetic crossing studies revealed that a partial reduction of Drp1 is protective against mutant protein(s)-induced mitochondrial and synaptic toxicities. Based on findings from cell cultures, mouse models and postmortem brains of AD and other neurodegenerative disease, we cautiously conclude that reduced Drp1 is a promising therapeutic target for AD and other neurological diseases.

    Original languageEnglish (US)
    JournalCells
    Volume8
    Issue number9
    DOIs
    StatePublished - Aug 23 2019

    Keywords

    • Alzheimer’s disease
    • Huntington’s disease
    • Parkinson’s disease
    • aging
    • diabetes
    • dynamin-related protein 1
    • mitochondria
    • mitochondrial division inhibitor
    • obesity

    ASJC Scopus subject areas

    • Medicine(all)

    Fingerprint

    Dive into the research topics of 'Dynamics of Dynamin-Related Protein 1 in Alzheimer's Disease and Other Neurodegenerative Diseases'. Together they form a unique fingerprint.

    Cite this