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
Citations
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Non-coding RNAs: New players in mitophagy and neurodegeneration
Robert G. Burgess,Hongtao Wang +1 more
TL;DR: In this paper , the authors reviewed the major mitophagy pathways modulated by some classical and newly found non-coding RNAs and summarized the diverse mechanisms in a regulatory network.
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Omics-based biomarkers discovery for Alzheimer's disease
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Biomarkers of aging
Hà Dương Xuân Bảo,Jiani Cao,Mengting Chen,Min Chen,Wei Chen,Xiao Chen,Yanhao Chen,Yu Chen,Yutian Chen,Zhiyang Chen,Jagadish K. Chhetri,Yingjie Ding,Junlin Feng,Jun Guo,Mengmeng Guo,Chuting He,Yujuan Jia,Haiping Jiang,Ying Jing,Dingfeng Li,Jiaming Li,Jingyi Li,Qinhao Liang,Rui Liang,Xiaoqian Liu,Zuojun Liu,Oscar Junhong Luo,Jianwei Lv,Jingyi Ma,Jiawei Nie,Xinhua Qiao,Xinpei Sun,Xiaoqiang Tang,Jianfang Wang,Qiaoran Wang,Siyuan Wang,Xuan Wang,Yaning Wang,Yuhan Wang,Kai Xia,Fuhui Liao,Lingyan Xu,Yingying Xu,Haoteng Yan,Liang Yang,Ruici Yang,Yuanxin Yang,Yilin Ying,Le Zhang,Weiwei Zhang,Wenwan Zhang,Xuning Zhang,Zhuo Zhang,Min Zhou,Rui Zhou,Qingchen Zhu,Zhengmao Zhu,Feng Cao,Zhongwei Cao,P. Chang,Chang Chen,Guobing Chen,Hou-Zao Chen,Jun Chen,Weimin Ci,Bi-Sen Ding,Qiurong Ding,Feng Gao,J.H. Han,Kai Huang,Zhenyu Ju,Qing-Peng Kong,Ji Li,Jian Li,Xin Li,Baohua Liu,Feng Liu,Lin Liu,Qiang Liu,Qiang Liu,Xingguo Liu,Yong Liu,Xianghang Luo,Shuai Ma,Xinran Ma,Zhiyong Mao,Jing Nie,Yaojin Peng,Jing Qu,Jie Ren,Ruibao Ren,Moshi Song,Zhou Songyang,Yi E. Sun,Mei Tian,Sheng Wang,Si Qi Wang,Xia Wang,Xiaoning Wang,Yan-Jiang Wang,Yunfang Wang,Catherine C L Wong,Andy Peng Xiang,Yichuan Xiao,Zhengwei Xie,Daichao Xu,Jing Ye,Rui Yue,Cuntai Zhang,Hongbo Zhang,Liang Zhang,Weiqi Zhang,Yong Zhang,Yun-wu Zhang,Zhuohua Zhang,Tongbiao Zhao,Yuzheng Zhao,Dahai Zhu,Weiguo Zou,Gang Pei,Guang-Hui Liu +120 more
TL;DR: Aging biomarkers are a combination of biological parameters to assess agerelated changes, track the physiological aging process, and predict the transition into a pathological status as discussed by the authors , which can help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower?
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High-frequency and functional mitochondrial DNA mutations at the single-cell level
Xiaoxian Guo,Weilin Xu,Weiping Zhang,Cuiping Pan,Anna E. Thalacker-Mercer,Hong-Xiang Zheng,Zhenglong Gu +6 more
TL;DR: In this article , the prevalence of high-frequency pathogenic mutations at the single-cell level was investigated and the diversity of singlecell mtDNA mutations that were previously underappreciated was demonstrated.
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Visualizing, quantifying and manipulating mitochondrial DNA in vivo.
TL;DR: This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify and manipulate the properties of mtDNA within cells.
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