Lili Li, Shiyin Li, Lei Cai, Xiaofeng Yang, Yifeng Feng, Liying Zhang, Xiaofei He, Mingyue Li
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Physical exercise mitigates the cognitive impairments by promoting ER-phagy in mice model of Alzheimer's disease.
Alzheimer's disease (AD) is the primary cause of dementia in older individuals, exhibiting an increasing incidence worldwide. Endoplasmic reticulum (ER) quality control has been receiving attention in the pathology of AD. The accumulation of misfolded proteins in the ER will activates the unfolded protein response (UPR), leading to cellular apoptosis. Using a mouse model of 5xFAD, we found that physical exercise (PE) promoted the clearance of ER fragments and inhibited the ER stress via ER autophagy (ER - Phagy). As a result, physical exercise reduced Aβ deposition, inhibited the neuronal apoptosis, ameliorated the emotional and cognitive impairments. Mechanistically, these PE related effects may be linked to the increased FAM134B, an ER-Phagy receptor, by up-regulating neuronal progranulin (Pgrn). Recombinant Pgrn injection could mimic the protective effects of PE, whereas down-regulation of Pgrn could abolish the PE-associated protection. Our findings indicate that physical exercise, as a readily accessible lifestyle intervention, holds significant potential for preventing diseases related to the global aging population.
期刊介绍：
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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