Abstract
To date, the beta amyloid (Aβ) cascade hypothesis remains the main pathogenetic model of Alzheimers disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria in the cascade of events leading to AD, and we will try to provide an answer to the question “what comes first”.
Keywords: Alzheimer's disease, haplogroups, mitochondria, mtDNA, neurodegeneration
Current Alzheimer Research
Title: Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?
Volume: 5 Issue: 5
Author(s): Michelangelo Mancuso, Daniele Orsucci, Gabiele Siciliano and Luigi Murri
Affiliation:
Keywords: Alzheimer's disease, haplogroups, mitochondria, mtDNA, neurodegeneration
Abstract: To date, the beta amyloid (Aβ) cascade hypothesis remains the main pathogenetic model of Alzheimers disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria in the cascade of events leading to AD, and we will try to provide an answer to the question “what comes first”.
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Cite this article as:
Mancuso Michelangelo, Orsucci Daniele, Siciliano Gabiele and Murri Luigi, Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?, Current Alzheimer Research 2008; 5 (5) . https://dx.doi.org/10.2174/156720508785908946
DOI https://dx.doi.org/10.2174/156720508785908946 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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