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Br J Pharmacol. 2019 Sep;176(18):3489-3507. doi: 10.1111/bph.14585. Epub 2019 Mar 6.

Mitochondrial dysfunction in Alzheimer's disease: Role in pathogenesis and novel therapeutic opportunities.

Author information

1
University of Kansas Alzheimer's Disease Center, Fairway, KS, USA.
2
Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
3
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
4
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA.

Abstract

Dysfunction of cell bioenergetics is a common feature of neurodegenerative diseases, the most common of which is Alzheimer's disease (AD). Disrupted energy utilization implicates mitochondria at its nexus. This review summarizes some of the evidence that points to faulty mitochondrial function in AD and highlights past and current therapeutic development efforts. Classical neuropathological hallmarks of disease (β-amyloid and τ) and sporadic AD risk genes (APOE) may trigger mitochondrial disturbance, yet mitochondrial dysfunction may incite pathology. Preclinical and clinical efforts have overwhelmingly centred on the amyloid pathway, but clinical trials have yet to reveal clear-cut benefits. AD therapies aimed at mitochondrial dysfunction are few and concentrate on reversing oxidative stress and cell death pathways. Novel research efforts aimed at boosting mitochondrial and bioenergetic function offer an alternative treatment strategy. Enhancing cell bioenergetics in preclinical models may yield widespread favourable effects that could benefit persons with AD. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

PMID:
30675901
PMCID:
PMC6715612
[Available on 2020-09-01]
DOI:
10.1111/bph.14585

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