Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms

Research output: Contribution to journalReviewResearchpeer-review

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

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.

Original languageEnglish
JournalTrends in Neurosciences
Volume40
Issue number3
Pages (from-to)151-166
Number of pages16
ISSN0166-2236
DOIs
Publication statusPublished - 2017

ID: 188451689