title: 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.
authors.affiliation: Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Reginald C
authors.initials: RC
authors.lastname: Adiele
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria.
authors.forename: Chiedukam A
authors.initials: CA
authors.lastname: Adiele
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000209:etiology*; D016874:Neurofibrillary Tangles / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; amyloid-beta; mitochondria; neurofibrillary tangles; neuronal death; oxidative stress