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One of the AD pathological factors, \u03b2-Amyloid (A\u03b2), 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\u03b2-induced microglial activation and behavioral deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The AD mouse model was crossed with\n                      <jats:italic>Clec5a<\/jats:italic>\n                      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\u03b2 deposition and microglia recruitment were identified by ELISA and immunohistochemistry. The inflammatory signals were identified by ELISA and western blotting. In the\n                      <jats:italic>Clec5a<\/jats:italic>\n                      knockdown microglial cell model and\n                      <jats:italic>Clec5a<\/jats:italic>\n                      knockout primary microglia, the microglial phagocytosis was revealed using the fluorescent-labeled A\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The AD mice with\n                      <jats:italic>Clec5a<\/jats:italic>\n                      knockout improved A\u03b2-induced memory deficit and abnormal nociception. These mice have reduced A\u03b2 deposition and increased microglia coverage surrounding the amyloid plaque, suggesting the involvement of CLEC5A in AD progression and A\u03b2 clearance. Moreover, the phagocytosis was also increased in the A\u03b2-stressed\n                      <jats:italic>Clec5a<\/jats:italic>\n                      knockdown microglial cell lines and\n                      <jats:italic>Clec5a<\/jats:italic>\n                      knockout primary microglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>Clec5a<\/jats:italic>\n                      knockout ameliorates AD-like deficits by modulating microglial A\u03b2 clearance. This study implies that targeting microglial\n                      <jats:italic>Clec5a<\/jats:italic>\n                      could offer a promising approach to mitigate AD progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-024-03253-x","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T04:02:47Z","timestamp":1729656167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial A\u03b2 clearance in Alzheimer\u2019s disease mouse model"],"prefix":"10.1186","volume":"21","author":[{"given":"Yu-Yi","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Han","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shie-Liang","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene Han-Juo","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"3253_CR1","doi-asserted-by":"crossref","unstructured":"Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. 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