Multi-omics studies reveal ameliorating effects of physical exercise on neurodegenerative diseases

Guo, Yuhuai; Wang, Shouli; Chao, Xiaowen; Li, Ding; Wang, Ying; Guo, Qihao; Chen, Tianlu

doi:10.3389/fnagi.2022.1026688

Cited by 10 publications

(4 citation statements)

References 124 publications

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“…Compelling evidence suggests impaired cholesterol synthesis within the brain of AD patients [ 29 ], and intriguingly, abnormal deposition of cholesterol within tangled neurons has been observed in individuals with AD [ 6 ]. It is well known that exercise is an effective means of preventing neurodegenerative diseases [ 42 ]. Our prior investigation has elucidated that aerobic exercise has the capacity to enhance the density of cortical and hippocampal dendritic spines while concurrently mitigating the anomalous deposition of Aβ in the brain of APP/PS1 mice [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice

Yuan

Tong

et al. 2023

IJMS

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Impaired cholesterol synthesizing ability is considered a risk factor for the development of Alzheimer’s disease (AD), as evidenced by reduced levels of key proteases in the brain that mediate cholesterol synthesis; however, cholesterol deposition has been found in neurons in tangles in the brains of AD patients. Although it has been shown that statins, which inhibit cholesterol synthesis, reduce the incidence of AD, this seems paradoxical for AD patients whose cholesterol synthesizing capacity is already impaired. In this study, we aimed to investigate the effects of aerobic exercise on cholesterol metabolism in the brains of APP/PS1 mice and to reveal the mechanisms by which aerobic exercise improves cognitive function in APP/PS1 mice. Our study demonstrates that the reduction of SEC24D protein, a component of coat protein complex II (COPII), is a key factor in the reduction of cholesterol synthesis in the brain of APP/PS1 mice. 12 weeks of aerobic exercise was able to promote the recovery of SEC24D protein levels in the brain through activation of protein kinase B (AKT), which in turn promoted the expression of mem-brane-bound sterol regulatory element-binding protein 2 (SREBP2) nuclear translocation and the expression of key proteases mediating cholesterol synthesis. Simultaneous aerobic exercise restored cholesterol transport capacity in the brain of APP/PS1 mice with the ability to efflux excess cholesterol from neurons and reduced neuronal lipid rafts, thereby reducing cleavage of the APP amyloid pathway. Our study emphasizes the potential of restoring intracerebral cholesterol homeostasis as a therapeutic strategy to alleviate cognitive impairment in AD patients.

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Section: Discussionmentioning

confidence: 99%

Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice

Yuan

Tong

et al. 2023

IJMS

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“…The divergence of gut microbiota composition between the APP/PS1 and wild-type mice was proved to start at a young age (1-3 months), before the detection of amyloid deposition, which suggested that gut bacteria alteration could aid the early detection of AD prior to pathological evidence. 86 87 Microbial metabolites associated with AD mainly include bile acids, 88 short-chain fatty acids, 89 branchedchain amino acids, indole and pyrimidine, 90 and steroid hormones. 91 Their catabolism and synthesis are regulated by the structure and function of gut microbiota.…”

Section: Urine Testsmentioning

confidence: 99%

Consensus on rapid screening for prodromal Alzheimer’s disease in China

Huang,

Li,

et al. 2024

Gen Psych

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Alzheimer’s disease (AD) is a common cause of dementia, characterised by cerebral amyloid-β deposition, pathological tau and neurodegeneration. The prodromal stage of AD (pAD) refers to patients with mild cognitive impairment (MCI) and evidence of AD’s pathology. At this stage, disease-modifying interventions should be used to prevent the progression to dementia. Given the inherent heterogeneity of MCI, more specific biomarkers are needed to elucidate the underlying AD’s pathology. Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD’s pathology, their clinical applications are limited by their high costs and invasiveness, particularly in low-income areas in China. Therefore, to improve the early detection of Alzheimer's disease (AD) pathology through cost-effective screening methods, a panel of 45 neurologists, psychiatrists and gerontologists was invited to establish a formal consensus on the screening of pAD in China. The supportive evidence and grades of recommendations are based on a systematic literature review and focus group discussion. National meetings were held to allow participants to review, vote and provide their expert opinions to reach a consensus. A majority (two-thirds) decision was used for questions for which consensus could not be reached. Recommended screening methods are presented in this publication, including neuropsychological assessment, peripheral biomarkers and brain imaging. In addition, a general workflow for screening pAD in China is established, which will help clinicians identify individuals at high risk and determine therapeutic targets.

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“…While physical and mental exercises enhance oxygen consumption and may generate the oxidative redox potential needed for proper folding of these proteins ( Figure 1 ). A prospective cohort study indicated that frequent exercises, housework-related activities, and friend/family visits were associated with a reduced risk of multiple types of dementia (Guo et al, 2022 ; Zhu et al, 2022 ).…”

Section: Lysosomal Overloading Hypothesismentioning

confidence: 99%