Molecular Basis of Alzheimer’s Disease: Focus on Mitochondria
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by memory loss and multiple cognitive impairments. With the increased aging population, AD is a major health concern in society. Morphological and pathological studies revealed that AD is associated with the loss of synapses, defective mitochondria, and the proliferation of reactive astrocytes and microglia, in addition to the presence amyloid-β and phosphorylated tau in learning and memory regions of the brain in AD patients. AD occurs in two forms: early-onset familial and late-onset sporadic. Genetic mutations in APP, PS1, and PS2 loci cause familial AD. Multiple factors are reported to be involved in late-onset AD, including APOE4 genotype, polymorphisms in several gene loci and type 2 diabetes, traumatic brain injury, stroke, and age-related factors, including increased reactive oxygen species production and dysfunction in mitochondria. It is widely accepted that synaptic damage and mitochondrial dysfunction are early events in disease process. The purpose of this article is to highlight molecular triggers to the disease process. This article also reviews factors, including age, gender, lifestyle, epigenetic factors, and type 2 diabetes, that are involved in late-onset AD. This article also discusses recent developments in research of mitochondrial structure, function, physiology, dynamics, biogenesis, mitophagy, and mitochondrial DNA changes in healthy and diseased states.
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S-Nitrosylation of the GTPase activity region of Drp-1 leads to loss of activity and, in a mutant APP/PS1 transgenic mouse model of AD, leads to neurotoxicity.
“Among the various PTMs, S-Nitrosylation of the GTPase activity region of Drp-1 leads to a loss of activity and in a mutant APP/PS1 transgenic mouse model of AD, it leads to neurotoxicity [39].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [39]
Drp-1 is critically important for mitochondrial fission, but when its expression is lowered, there is some evidence that Drp-1 may play a role in mitochondrial fusion as well.
“Drp-1 is critically important for mitochondrial fission, but when its expression is lowered, there is some evidence that Drp-1 may play a role in mitochondria fusion as well [39].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [39]
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- Authors
- Oliver, D. M. A., & Reddy, P. H.
- Affiliations
- Texas Tech University (US)
- Corresponding author
- Reddy, P. Hemachandra
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2019-12-27
- Volume
- 72
- Issue
- s1
- Pages
- S95-S116
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2923937720
- Cited by
- 120
- References
- 67
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 18 · 2023: 12 · 2022: 18 · 2021: 18 · 2020: 21 · 2019: 6
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R41AG060836, R01AG042178, R01AG047812)
- National Institute of Neurological Disorders and Stroke (R01NS105473)
- 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
- MeSH terms
- Alzheimer Disease, Animals, Brain, DNA, Mitochondrial, Humans, Mitochondria, Phosphorylation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apolipoprotein E4
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