The disease progression of neurodegenerative disorders (NDD), including Alzheimer's, Parkinson's and Huntington's disease, is inextricably tied to mitochondrial dysfunction. However, although the contribution by nuclear gene mutations is recognised for familial onset of NDD, the degree to which cytoplasmic inheritance serves as a predetermining factor for the predisposition and onset of NDD is not yet fully understood. We review the reproductive mechanisms responsible for ensuring a healthy mitochondrial population within each new generation and elucidate how advanced maternal age can constitute an increased risk for the onset of NDD in the offspring, through the increased heteroplasmic burden. On the one hand, this review draws attention to how assisted reproductive technologies (ART) can impair mitochondrial fitness in offspring. On the other hand, we consider qualified ART approaches as a significant tool for the prevention of NDD pathogenesis.

• MeSH
• cvičení MeSH
• lidé MeSH
• mitochondrie genetika   MeSH
• neurodegenerativní nemoci * genetika   MeSH
• progrese nemoci MeSH
• rozmnožování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease and the most common cause of dementia among older adults. There are no effective treatments available for the disease, and it is associated with great societal concern because of the substantial costs of providing care to its sufferers, whose numbers will increase as populations age. While multiple causes have been proposed to be significant contributors to the onset of sporadic AD, increased age is a unifying risk factor. In addition to amyloid-β (Aβ) and tau protein playing a key role in the initiation and progression of AD, impaired mitochondrial bioenergetics and dynamics are likely major etiological factors in AD pathogenesis and have many potential origins, including Aβ and tau. Mitochondrial dysfunction is evident in the central nervous system (CNS) and systemically early in the disease process. Addressing these multiple mitochondrial deficiencies is a major challenge of mitochondrial systems biology. We review evidence for mitochondrial impairments ranging from mitochondrial DNA (mtDNA) mutations to epigenetic modification of mtDNA, altered gene expression, impaired mitobiogenesis, oxidative stress, altered protein turnover and changed organelle dynamics (fission and fusion). We also discuss therapeutic approaches, including repurposed drugs, epigenetic modifiers, and lifestyle changes that target each level of deficiency which could potentially alter the course of this progressive, heterogeneous Disease while being cognizant that successful future therapeutics may require a combinatorial approach.

• Klíčová slova
• Alzheimer's disease, bioenergetics, epigenetic modifiers, lifestyle changes, mitochondria, mtDNA, repurposed drugs., β-amyloid,
• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• lidé MeSH
• mitochondriální DNA metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• neurodegenerativní nemoci * metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• mitochondriální DNA MeSH