Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease
Evandro Fei Fang,Yujun Hou,Konstantinos Palikaras,Bryan A. Adriaanse,Jesse S. Kerr,Beimeng Yang,Sofie Lautrup,Mahdi Hasan-Olive,Domenica Caponio,Xiuli Dan,P Rocktäschel,Deborah L. Croteau,Mansour Akbari,Nigel H. Greig,Tormod Fladby,Hilde Nilsen,M Z Cader,Mark P. Mattson,Nektarios Tavernarakis,Nektarios Tavernarakis,Vilhelm A. Bohr,Vilhelm A. Bohr +21 more
TLDR
Evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models is provided, suggesting that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and thatMitophagy represents a potential therapeutic intervention.Abstract:
Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways. Mitophagy diminishes insoluble Aβ1-42 and Aβ1-40 and prevents cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolishes AD-related tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic tau nematodes and mice. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and that mitophagy represents a potential therapeutic intervention.read more
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Tau Oligomers Neurotoxicity
TL;DR: A review of the most recent literature on the damaging effect of TauOs on the stability of the genome and the function of the nucleus, energy production and mitochondrial function, cell signaling and synaptic plasticity, the microtubule assembly, neuronal cytoskeleton and axonal transport, and the effectiveness of the protein degradation system is presented in this article.
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Mitochondrial turnover and homeostasis in ageing and neurodegeneration.
TL;DR: The mechanisms regulating mitochondrial number in cells are surveyed, with particular emphasis on neurons, and recent findings implicating perturbation of mitochondrial homeostasis in cellular senescence and organismal ageing as well as in age-associated neurodegenerative diseases are discussed.
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Targeting Mitochondrial Network Architecture in Down Syndrome and Aging.
Nunzia Mollo,Rita Cicatiello,Miriam Aurilia,Roberta Scognamiglio,Rita Genesio,Maria Charalambous,Simona Paladino,Anna Conti,Lucio Nitsch,Lucio Nitsch,Antonella Izzo +10 more
TL;DR: Evidence is summarized suggesting that drugs targeting either PGC-1α/PPARGC1A or mTOR signaling or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function.
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Urolithin A suppresses RANKL-induced osteoclastogenesis and postmenopausal osteoporosis by, suppresses inflammation and downstream NF-κB activated pyroptosis pathways
Huaqiang Tao,Wenming Li,Wei Zhang,Chen Yang,Chun Zhang,Xiaolong Liang,Juan Yin,Jiaxiang Bai,Gaoran Ge,Haifeng Zhang,Xing Yang,Hongxia Li,Yaozeng Xu,Yuefeng Hao,Yu Liu,Dechun Geng +15 more
TL;DR: In this article, the effect of urolithin A (UA) administration on osteoporosis progression in the context of estrogen deficiency-induced bone loss was investigated, and in vivo results indicated that UA effectively reduced ovariectomy-induced systemic bone loss.
Journal ArticleDOI
A natural product solution to aging and aging-associated diseases.
Chuanbin Yang,Wei Zhang,Xiaoduo Dong,Chunjin Fu,Jimin Yuan,Menglong Xu,Zhen Liang,Chen Qiu,Chengchao Xu,Chengchao Xu +9 more
TL;DR: It is argued that natural products might eventually provide a solution to aging and aging-associated diseases and extend healthspan and/or lifespan.
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