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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Unraveling the Roles of Protein Kinases in Autophagy: An Update on Small-Molecule Compounds for Targeted Therapy.
TL;DR: This Perspective focuses on summarizing the different roles of protein kinases, including positive, negative, and bidirectional regulations of autophagy, and discusses several small-molecule compounds targeting theseprotein kinases in human diseases, highlighting their pivotal roles in autophagic for targeted therapeutic purposes.
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Peripheral Auditory Nerve Impairment in a Mouse Model of Syndromic Autism
TL;DR: In this article , a mouse model of the MEF2C haploinsufficiency syndrome (Mef2c-Het) was used to evaluate peripheral auditory nerve (AN) function and the impact of peripheral AN deficits with minimal hearing loss.
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Iron out, mitophagy in! A way to slow down hepatocellular carcinoma
TL;DR: It is demonstrated that induction of mitophagy via iron depletion suppresses the development of hepatocellular carcinoma (HCC), and this work suggests turning upMitophagy as a potential therapeutic strategy against liver cancer.
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MoNET: an R package for multi-omic network analysis.
TL;DR: Yan as mentioned in this paper integrated the relationship between SNPs, genes/proteins and metabolites, and developed an R package MoNET for multi-omic network analysis, enabling users to not only track down the interaction of SNPs/genes with metabolome level, but also trace back for the potential risk variants/regulators given altered genes/metabolites.
Book ChapterDOI
Autophagic processes in early- and late-onset Alzheimer's disease
Chenglong Xie,Yahyah Aman,Johannes Frank,Maria Jose Donate-Lagartos,Ruben Gudmundsrud,Kateřina Čechová,Liu Shi,Martin Vyhnalek,Evandro Fei Fang +8 more
TL;DR: This chapter reviews the extant literature on autophagy in AD and covers recent progress on the molecular mechanisms of NAD+-dependent mitophagy/autophagy regulation and mechanisms underlying the anti-AD potential of NAD+.
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