title: Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms.
abstract: Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged mitochondria (mitophagy) is also compromised in AD, resulting in the accumulation of dysfunctional mitochondria. Results in animal and cellular models of AD and in patients with sporadic late-onset AD suggest that impaired mitophagy contributes to synaptic dysfunction and cognitive deficits by triggering Aβ and Tau accumulation through increases in oxidative damage and cellular energy deficits; these, in turn, impair mitophagy. Interventions that bolster mitochondrial health and/or stimulate mitophagy may therefore forestall the neurodegenerative process in AD.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Kerr
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Adriaanse
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: M Zameel
authors.initials: MZ
authors.lastname: Cader
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Danish Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: BohrV@grc.nia.nih.gov.
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: evandro.fang@nih.gov.
authors.forename: Evandro F
authors.initials: EF
authors.lastname: Fang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology*