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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The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review
Niklas Reich,Christian Hölscher +1 more
TL;DR: The neuroprotective pathways that are induced following GLP-1R activation in neurons, microglia and astrocytes include synaptic protection, improvements in cognition, learning and motor function, amyloid pathology-ameliorating properties and the suppression of Ca2+ deregulation and ER stress.
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Rab7a and Mitophagosome Formation.
Esther Hui Na Tan,Bor Luen Tang +1 more
TL;DR: The small GTPase, Rab7a, and the regulators of its GDP/GTP-binding status were shown to have roles in both endocytic membrane traffic and autophagy, and recent findings on PTEN-induced kinase 1 (PINK1)-Parkin mediated mitophagy are discussed.
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Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle.
TL;DR: Vitamin B12 supplementation of B12-deficient adult Aβ animals is beneficial, demonstrating potential for vitamin B12 as a therapy to target pathogenic features of AD triggered by proteotoxic stress.
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Autophagy in the mammalian nervous system: a primer for neuroscientists.
Fumi Suomi,Thomas G. McWilliams +1 more
TL;DR: This minireview focuses on established and emerging concepts in the field, paying particular attention to the physiological significance of macroautophagy and the burgeoning world of selective autophagy pathways in the context of the vertebrate nervous system.
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Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum–Mitochondria Contact and Mitochondrial Functions in Stress-induced Hypertension Rats
Kokwin Ooi,Li Hu,Yi Feng,Chengzhi Han,Xiaorong Ren,Xinyi Qian,Haofeng Huang,Sijia Chen,Qi Shi,Hong Lin,Jijiang Wang,Danian Zhu,Rui Wang,Chunmei Xia +13 more
TL;DR: Sigma-1 receptor activation suppresses microglia M1 polarization and neuroinflammation via regulating endoplasmic reticulum–mitochondria contact and mitochondrial functions in stress-induced hypertension rats and ameliorates sympathetic hyperactivity in Stress-induced hypertensive rats.
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