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

doi:10.1016/j.tins.2017.01.002

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

^*Corresponding author for this work

202 Citations (Scopus)

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.

Original language	English
Journal	Trends in Neurosciences
Volume	40
Issue number	3
Pages (from-to)	151-166
Number of pages	16
ISSN	0166-2236
DOIs	https://doi.org/10.1016/j.tins.2017.01.002
Publication status	Published - 2017

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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.",

author = "Kerr, {Jesse S.} and Adriaanse, {Bryan A.} and Greig, {Nigel H.} and Mattson, {Mark P.} and Cader, {M. Zameel} and Bohr, {Vilhelm A.} and Fang, {Evandro F.}",

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pages = "151--166",

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TY - JOUR

T1 - Mitophagy and Alzheimer's Disease

T2 - Cellular and Molecular Mechanisms

AU - Kerr, Jesse S.

AU - Adriaanse, Bryan A.

AU - Greig, Nigel H.

AU - Mattson, Mark P.

AU - Cader, M. Zameel

AU - Bohr, Vilhelm A.

AU - Fang, Evandro F.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1016/j.tins.2017.01.002

DO - 10.1016/j.tins.2017.01.002

M3 - Review

C2 - 28190529

AN - SCOPUS:85012907718

SN - 0378-5912

VL - 40

SP - 151

EP - 166

JO - Trends in Neurosciences

JF - Trends in Neurosciences

IS - 3

ER -

Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms

Abstract

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