Mitochondrial Regulatory Pathways in the Pathogenesis of Alzheimer's Disease
- PMID: 27392851
- DOI: 10.3233/JAD-150967
Mitochondrial Regulatory Pathways in the Pathogenesis of Alzheimer's Disease
Abstract
Alzheimer's disease (AD) is an age-associated neurodegenerative brain disorder with progressive cognitive decline that leads to terminal dementia and death. For decades, amyloid-beta (Aβ) and neurofibrillary tangle (NFT) aggregation hypotheses have dominated studies on the pathogenesis and identification of potential therapeutic targets in AD. Little attention has been paid to the mitochondrial molecular/biochemical pathways leading to AD. Mitochondria play a critical role in cell viability and death including neurons and neuroglia, not only because they regulate energy and oxygen metabolism but also because they regulate cell death pathways. Mitochondrial impairment and oxidative stress are implicated in the pathogenesis of AD. Interestingly, current therapeutics provide symptomatic benefits to AD patients resulting in the use of preventive trials on presymptomatic subjects. This review article elucidates the pathophysiology of AD and emphasizes the need to explore the mitochondrial pathways to provide solutions to unanswered questions in the prevention and treatment of AD.
Keywords: Alzheimer’s disease; amyloid-beta; mitochondria; neurofibrillary tangles; neuronal death; oxidative stress.
Similar articles
-
Mitochondrial Dysfunction Triggers Synaptic Deficits via Activation of p38 MAP Kinase Signaling in Differentiated Alzheimer's Disease Trans-Mitochondrial Cybrid Cells.J Alzheimers Dis. 2017;59(1):223-239. doi: 10.3233/JAD-170283. J Alzheimers Dis. 2017. PMID: 28598851 Free PMC article.
-
Impaired transcription in Alzheimer's disease: key role in mitochondrial dysfunction and oxidative stress.J Alzheimers Dis. 2013;34(1):115-31. doi: 10.3233/JAD-121444. J Alzheimers Dis. 2013. PMID: 23364141 Review.
-
Alzheimer's disease.Subcell Biochem. 2012;65:329-52. doi: 10.1007/978-94-007-5416-4_14. Subcell Biochem. 2012. PMID: 23225010 Review.
-
Plaques and tangles and the pathogenesis of Alzheimer's disease.Folia Neuropathol. 2006;44(1):1-11. Folia Neuropathol. 2006. PMID: 16565925 Review.
-
Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression.Hum Mol Genet. 2006 May 1;15(9):1437-49. doi: 10.1093/hmg/ddl066. Epub 2006 Mar 21. Hum Mol Genet. 2006. PMID: 16551656
Cited by
-
Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer's Disease male mice.Mol Psychiatry. 2023 Aug;28(8):3332-3342. doi: 10.1038/s41380-023-02135-7. Epub 2023 Jun 28. Mol Psychiatry. 2023. PMID: 37369719 Free PMC article.
-
Reply to Pluta, R. Comment on "Minich et al. Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients 2022, 14, 3934".Nutrients. 2023 Mar 21;15(6):1507. doi: 10.3390/nu15061507. Nutrients. 2023. PMID: 36986237 Free PMC article.
-
Are mitophagy enhancers therapeutic targets for Alzheimer's disease?Biomed Pharmacother. 2022 May;149:112918. doi: 10.1016/j.biopha.2022.112918. Epub 2022 Apr 4. Biomed Pharmacother. 2022. PMID: 35585708 Free PMC article. Review.
-
Rhein Ameliorates Cognitive Impairment in an APP/PS1 Transgenic Mouse Model of Alzheimer's Disease by Relieving Oxidative Stress through Activating the SIRT1/PGC-1α Pathway.Oxid Med Cell Longev. 2022 Mar 22;2022:2524832. doi: 10.1155/2022/2524832. eCollection 2022. Oxid Med Cell Longev. 2022. PMID: 35360200 Free PMC article.
-
Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases.Biomedicines. 2021 Oct 29;9(11):1574. doi: 10.3390/biomedicines9111574. Biomedicines. 2021. PMID: 34829803 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical