Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms

Jesse S. Kerr, Bryan A. Adriaanse, Nigel H. Greig, Mark P. Mattson, M. Zameel Cader, Vilhelm A. Bohr, Evandro F. Fang

Research output: Contribution to journalArticlepeer-review

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. Mitochondrial homeostasis is important for synaptic plasticity, learning, and memory.Neurons affected in Alzheimer's disease (AD) exhibit dysfunctional mitochondria.Mitophagy plays important roles in mitochondrial homeostasis, neuroprotection, and resistance to neurodegeneration.Induced pluripotent stem cell-derived neurons and animal models of sporadic AD provide powerful tools to investigate mitochondrial dysfunction and mitophagy.NAD+ depletion and impaired mitophagy may occur early in AD and contribute to synaptic dysfunction and neuronal degeneration.

Original languageEnglish (US)
JournalTrends in Neurosciences
DOIs
StateAccepted/In press - 2017

ASJC Scopus subject areas

  • Neuroscience(all)

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