TY - JOUR
T1 - Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer's disease neurodegeneration
AU - Casoli, Tiziana
AU - Spazzafumo, Liana
AU - Di Stefano, Giuseppina
AU - Conti, Fiorenzo
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aging
KW - Allele
KW - Alzheimer's disease
KW - Heteroplasmy
KW - MitoChip
KW - mtDNA
KW - Mutation
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U2 - 10.3389/fnagi.2015.00142
DO - 10.3389/fnagi.2015.00142
M3 - Article
AN - SCOPUS:84938598693
VL - 7
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - JUL
M1 - 142
ER -