國家衛生研究院 NHRI:Item 3990099045/16222
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    题名: The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Abeta clearance in Alzheimer's disease mouse model
    其它题名: The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Aβ clearance in Alzheimer's disease mouse model
    作者: Lin, YY;Chang, WH;Hsieh, SL;Cheng, IHJ
    贡献者: Immunology Research Center
    摘要: BackgroundAlzheimer's disease (AD) is a neurodegenerative disease that causes cognitive dysfunction in older adults. One of the AD pathological factors, beta-Amyloid (A beta), triggers inflammatory responses and phagocytosis of microglia. C-type lectin domain family 5 member A (CLEC5A) induces over-reactive inflammatory responses in several virus infections. Yet, the role of CLEC5A in AD progression remains unknown. This study aimed to elucidate the contribution of CLEC5A to A beta-induced microglial activation and behavioral deficits.MethodsThe AD mouse model was crossed with Clec5a knockout mice for subsequent behavioral and pathological tests. The memory deficit was revealed by the Morris water maze, while the nociception abnormalities were examined by the von Frey filament and hotplate test. The A beta deposition and microglia recruitment were identified by ELISA and immunohistochemistry. The inflammatory signals were identified by ELISA and western blotting. In the Clec5a knockdown microglial cell model and Clec5a knockout primary microglia, the microglial phagocytosis was revealed using the fluorescent-labeled A beta.ResultsThe AD mice with Clec5a knockout improved A beta-induced memory deficit and abnormal nociception. These mice have reduced A beta deposition and increased microglia coverage surrounding the amyloid plaque, suggesting the involvement of CLEC5A in AD progression and A beta clearance. Moreover, the phagocytosis was also increased in the A beta-stressed Clec5a knockdown microglial cell lines and Clec5a knockout primary microglia.ConclusionThe Clec5a knockout ameliorates AD-like deficits by modulating microglial A beta clearance. This study implies that targeting microglial Clec5a could offer a promising approach to mitigate AD progression.
    日期: 2024-10-23
    關聯: Journal of Neuroinflammation. 2024 Oct 23;21:Article number 273.
    Link to: http://dx.doi.org/10.1186/s12974-024-03253-x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1742-2094&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001339854100002
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85207479397
    显示于类别:[謝世良] 期刊論文

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