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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Protein degradation-associated mechanisms that are affected in Alzheimer´s disease
Angeles C. Tecalco-Cruz,José Pedraza-Chaverri,Alfredo Briones-Herrera,Eduardo Cruz-Ramos,Lilia López-Cánovas,Jesús Zepeda-Cervantes +5 more
TL;DR: This review investigated the ubiquitin-proteasome system, lysosome- associated degradation, endoplasmic-reticulum-associated degradation, and the formation of advanced glycation end products for Alzheimer's disease.
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Inhibition of miR-130b-3p restores autophagy and attenuates intervertebral disc degeneration through mediating ATG14 and PRKAA1
Tongde Wu,Xuebing Jia,Ziqi Zhu,Kaiwen Guo,Qiang Wang,Zhiqiang Gao,Xinhua Li,Yufeng Huang,Desheng Wu +8 more
TL;DR: The suppression of miR-130b-3p may become an effective therapeutic strategy for IVDD because it can upregulate the autophagic flux and alleviate the IVDD via targeting ATG14 and PRKAA1.
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ALS and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy
TL;DR: In this paper, the authors investigated how ALS-associated mutations in TANK-binding kinase 1 (TBK1) affect Parkin-dependent mitophagy using imaging to dissect the molecular mechanisms involved in clearing damaged mitochondria.
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PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy
TL;DR: It is found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of t Tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy.
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Natural products as pharmacological modulators of mitochondrial dysfunctions for the treatments of Alzheimer's disease: A comprehensive review.
TL;DR: In this article, a review of the potentials of NPs and their underlying molecular mechanisms against Alzheimer's disease via reducing or improving mitochondrial dysfunction is presented, which may open the window to speed up the development of innovative anti-AD drugs originated from natural products and improve upcoming AD therapeutics.
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