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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Book ChapterDOI
Mitophagy Impairments as Culprit of Alzheimer’s Disease
TL;DR: In this paper , the mechanism of different mitophagy pathways and the possible molecular defect leading to mitophagia impairment in Alzheimer's disease are discussed and a glimpse of different therapeutic approaches to enhance mitophathy in neurons of AD brain and combat such diseases is provided.
Journal ArticleDOI
Electroacupuncture Stimulation Suppresses Postoperative Inflammatory Response and Hippocampal Neuronal Injury
TL;DR: These findings indicated the POCD was the synergistic outcome of anaesthesia and surgical stimulation but with different pathogenic mechanism, and the protection of electroacupuncture form PocD after femoral fracture surgery is related to the inhibition of inflammation response and neuron impairment.
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Crosstalk between dietary pomegranate and gut microbiota: evidence of health benefits.
TL;DR: In this paper , the interplay between pomegranate and GM is thoroughly described by unveiling a dialog in which both actors seem to affect each other's roles, in which the influence of bioactive compounds from POMEgranate on GM is described.
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Modifiable risk factors of dementia linked to excitation-inhibition imbalance
Sina Hafizi,Tarek K. Rajji +1 more
TL;DR: In this paper , a conceptual model on the links between the modifiable risk factors and the E-I imbalance in dementia is proposed, which aims to address the current gap in the literature and facilitates future research on dementia prevention, discovery of new biomarkers, and developing new interventions.
Journal ArticleDOI
Mitophagy and long-term neuronal homeostasis.
TL;DR: In this article , the contribution of mitophagy, a selective form of autophagy that targets dysfunctional or superfluous mitochondria for degradation, in maintaining nervous system homeostasis is discussed.
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