Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?

Abstract

To date, the beta amyloid (Abeta) cascade hypothesis remains the main pathogenetic model of Alzheimer's 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 Abeta, 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".

Research progresses on flavonoids isolated from traditional Chinese medicine in treatment of Alzheimer's disease

“…Mitochondrial dysfunction has a certain impact on the pathogenesis of AD as indicated by impaired mitochondrial respiration observed in brain, platelets, and fibroblasts of AD patients (34). Energy failure, increased oxidative stress, and accumulation of Aβ could be caused by dysfunction of mitochondria, which would damage neurons and could explain many of the biochemical, genetic, and pathological features of sporadic AD (35).…”

“…Studies found that puerarin had potent effects in improving learning and memory disorders induced by scopolamine or D-galactose in a mouse model (65). Yan et al reported that puerarin protected neurons against apoptosis in the cortex and hippocampus of AD rats caused by Aβ [25][26][27][28][29][30][31][32][33][34][35] through downregulating Aβ and Bax expression in brain tissues, therefore alleviating the spatial learning and memory impairment of diseased animals (66). The anti-AD effects of puerarin were also suggested to be related to its abilities in decreasing the lipid peroxidase levels and increasing superoxide dismutase levels in brain tissues, enhancing cerebral blood flow, and improving brain microcirculation (67,68).…”

“…Studies on its active ingredients revealed that the total flavonoids extracted from the stem and leaf, mainly including scutellarin, baicalin, and chrysin, exhibited a series of pharmacological effects such as anti-inflammation, prevention from myocardial damage induced by ischemia-reperfusion, and improved cerebral ischemia (69,70). Regarding its effects against AD, Zuo et al found that total flavonoids of Baical Skullcap stem and leaf were capable of protecting hippocampal neurons against damage induced by injection of Aβ [25][26][27][28][29][30][31][32][33][34][35] in hippocampus in rat (71). The underlying mechanisms were related to its actions of decreasing the accumulation of lipid peroxide and proliferation of glial cells induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] (71).…”

“…Regarding its effects against AD, Zuo et al found that total flavonoids of Baical Skullcap stem and leaf were capable of protecting hippocampal neurons against damage induced by injection of Aβ [25][26][27][28][29][30][31][32][33][34][35] in hippocampus in rat (71). The underlying mechanisms were related to its actions of decreasing the accumulation of lipid peroxide and proliferation of glial cells induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] (71). Another study conducted by Ye et al demonstrated that the total flavonoids alleviated memory and learning injury and protected morphological change of hippocampal neurons in AD rats induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] injection (72).…”

“…The underlying mechanisms were related to its actions of decreasing the accumulation of lipid peroxide and proliferation of glial cells induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] (71). Another study conducted by Ye et al demonstrated that the total flavonoids alleviated memory and learning injury and protected morphological change of hippocampal neurons in AD rats induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] injection (72). These studies suggested the potential efficacies of total flavonoids of Baical Skullcap stem and leaf against AD.…”