Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration
Alzheimer’s disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the d...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-07-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00142/full |
| _version_ | 1811331139956113408 |
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| author | Tiziana eCasoli Liana eSpazzafumo Giuseppina eDi Stefano Fiorenzo eConti Fiorenzo eConti |
| author_facet | Tiziana eCasoli Liana eSpazzafumo Giuseppina eDi Stefano Fiorenzo eConti Fiorenzo eConti |
| author_sort | Tiziana eCasoli |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course. |
| first_indexed | 2024-04-13T16:14:43Z |
| format | Article |
| id | doaj.art-1e19521a2a434eaead42c58c45acd119 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T16:14:43Z |
| publishDate | 2015-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-1e19521a2a434eaead42c58c45acd1192022-12-22T02:40:05ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652015-07-01710.3389/fnagi.2015.00142145263Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegenerationTiziana eCasoli0Liana eSpazzafumo1Giuseppina eDi Stefano2Fiorenzo eConti3Fiorenzo eConti4INRCA IRCCSINRCA IRCCSINRCA IRCCSUniversita Politecnica delle MarcheINRCA IRCCSAlzheimer’s disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course.http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00142/fullAgingMutationAlzheimer’s diseasemitochondrial DNAallele |
| spellingShingle | Tiziana eCasoli Liana eSpazzafumo Giuseppina eDi Stefano Fiorenzo eConti Fiorenzo eConti Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration Frontiers in Aging Neuroscience Aging Mutation Alzheimer’s disease mitochondrial DNA allele |
| title | Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration |
| title_full | Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration |
| title_fullStr | Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration |
| title_full_unstemmed | Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration |
| title_short | Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer’s disease neurodegeneration |
| title_sort | role of diffuse low level heteroplasmy of mitochondrial dna in alzheimer s disease neurodegeneration |
| topic | Aging Mutation Alzheimer’s disease mitochondrial DNA allele |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00142/full |
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