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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Brain Mitochondrial Dysfunction: A Possible Mechanism Links Early Life Anxiety to Alzheimer’s Disease in Later Life
TL;DR: It is concluded that mitochondria might present as one of the novel therapeutic targets to block oxidative stress in patients with anxiety disorders to prevent AD in the early stage.
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Gefitinib facilitates PINK1/Parkin-mediated mitophagy by enhancing mitochondrial recruitment of OPTN
Ningning Li,Shan Sun,Guoqiang Ma,Hongyu Hou,Qilian Ma,Li Zhang,Zengli Zhang,Hongfeng Wang,Zheng Ying +8 more
TL;DR: In this paper , the authors show that gefitinib treatment promotes PINK1/Parkin-mediated mitophagy in both nonneuronal and neuronal cells, and this effect is independent of EGFR.
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Targeting the immune system towards novel therapeutic avenues to fight brain aging and neurodegeneration
TL;DR: Insight is provided into the current understanding of therapeutic targets that could be adopted to modulate the immune system, either systemically or locally, to defeat brain aging and neurodegeneration.
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Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging
Susmita Sil,Annadurai Thangaraj,Abiola O. Oladapo,Guoku Hu,Naseer A. Kutchy,Ke Liao,Shilpa Buch,Palsamy Periyasamy +7 more
TL;DR: In this article , the potential role of autophagy in the mechanism of neuroinflammaging in the context of HIV-1 and drug abuse was examined, and it was shown that impaired autophagia is associated with low-grade chronic inflammation and immune senescence, a known characteristic of pathological aging.
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Compromised autophagy and mitophagy in brain ageing and Alzheimer’s diseases
TL;DR: In this article , an overview of autophagy and mitophagia and their link to the progression of Alzheimer's disease is presented. But the authors do not discuss the effect of age-dependent compromised autophagias on brain health.
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