Cited by 260Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies

Open access
Onyango, Isaac G., Dennis, Jameel, Khan, Shaharyah M.·2016·Aging and Disease

Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by the progressive loss of cholinergic neurons, leading to the onset of severe behavioral, motor and cognitive impairments. It is a pressing public health problem with no effective treatment. Existing therapies only provide symptomatic relief without being able to prevent, stop or reverse the pathologic process. While the molecular basis underlying this multifactorial neurodegenerative disorder remains a significant challenge, mitochondrial dysfunction appears to be a critical factor in the pathogenesis of this disease. It is therefore important to target mitochondrial dysfunction in the prodromal phase of AD to slow or prevent the neurodegenerative process and restore neuronal function. In this review, we discuss mechanisms of action and translational potential of current mitochondrial and bioenergetic therapeutics for AD including: mitochondrial enhancers to potentiate energy production; antioxidants to scavenge reactive oxygen species and reduce oxidative damage; glucose metabolism and substrate supply; and candidates that target apoptotic and mitophagy pathways to remove damaged mitochondria. While mitochondrial therapeutic strategies have shown promise at the preclinical stage, there has been little progress in clinical trials thus far.

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Crossref · 10.14336/ad.2015.1007

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205 of 205 references verified0 citation errors · 0 not checkable

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  • Decrease in Δψm has been observed in several in vitro and in vivo AD models.

    “A decrease in Δψm (or mitochondrial depolarization) has been observed in several in vitro and in vivo AD models [65,66]”

    From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [65]

    The Mitochondrial Membrane Potential section (page unavailable) reports decreased Δψm in AD animal models and human cortical neurons studied ex vivo. This supports the animal-model finding, but the paper describes the neuronal evidence as ex vivo, not as a finding in several in vitro AD models. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • Mitochondrial dysfunction is heavily implicated in the ageing process and the pathogenesis of age-related diseases such as Alzheimer's disease.

    “Mitochondrial dysfunction is heavily implicated in the ageing process and the pathogenesis of age-related diseases such as Alzheimer's disease (AD) [16].”

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2 retracted

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Research works printed but not linked: 2

  1. [30]Medeiros DM (2008). Assessing mitochondria biogenesis. Methods, 46: 288- 294 18929661
  2. [38]Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al (2001). Mitochondrial abnormalities in Alzheimer's disease. J Neurosci, 21: 3017- 3023 11312286 PMC6762571

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Authors
Onyango, I. G., Dennis, J., & Khan, S. M.
Affiliations
Gencia (United States) (US)
Corresponding author
Onyango, Isaac G.
Venue
Aging and Disease
Published
2016
Volume
7
Issue
2
Pages
201
ISSN
2152-5250 (ISSN-L)
OpenAlex
W2321151839
Cited by
260
References
205
Citations by year
2026: 13 · 2025: 24 · 2024: 16 · 2023: 16 · 2022: 22 · 2021: 35 · 2020: 30 · 2019: 32 · 2018: 40 · 2017: 19 · 2016: 12
FWCI
4.03
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging and Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, mitochondrial dysfunction, bioenergetics, antioxidants, reactive oxygen species, glucose metabolism, substrate supply, apoptosis, mitophagy, neurodegeneration, cholinergic neurons, mitochondrial therapeutics

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