DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jung, Hyuncheol | ko |
dc.contributor.author | Lee, Se Young | ko |
dc.contributor.author | Lim, Seongjoon | ko |
dc.contributor.author | Choi, Hyeong Ryeol | ko |
dc.contributor.author | Choi, Yeseong | ko |
dc.contributor.author | Kim, Minjin | ko |
dc.contributor.author | Kim, Segi | ko |
dc.contributor.author | Lee, Yujean | ko |
dc.contributor.author | Han, Kyung Ho | ko |
dc.contributor.author | Chung, Won-Suk | ko |
dc.contributor.author | Kim, Chan Hyuk | ko |
dc.date.accessioned | 2022-10-05T07:00:44Z | - |
dc.date.available | 2022-10-05T07:00:44Z | - |
dc.date.created | 2022-08-15 | - |
dc.date.created | 2022-08-15 | - |
dc.date.issued | 2022-09 | - |
dc.identifier.citation | NATURE MEDICINE, v.28, no.9, pp.1802 - 1812 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | http://hdl.handle.net/10203/298832 | - |
dc.description.abstract | An engineered protein engages the efferocytosis pathway to induce amyloid-beta engulfment, resulting in behavioral rescue in Alzheimer's disease mouse models without the increased inflammation or vascular pathology associated with conventional antibody therapy Clearing amyloid-beta (A beta) through immunotherapy is one of the most promising therapeutic approaches to Alzheimer's disease (AD). Although several monoclonal antibodies against A beta have been shown to substantially reduce A beta burden in patients with AD, their effects on improving cognitive function remain marginal. In addition, a significant portion of patients treated with A beta-targeting antibodies experience brain edema and microhemorrhage associated with antibody-mediated Fc receptor activation in the brain. Here, we develop a phagocytosis inducer for A beta consisting of a single-chain variable fragment of an A beta-targeting monoclonal antibody fused with a truncated receptor binding domain of growth arrest-specific 6 (Gas6), a bridging molecule for the clearance of dead cells via TAM (TYRO3, AXL, and MERTK) receptors. This chimeric fusion protein (alpha A beta-Gas6) selectively eliminates A beta plaques through TAM receptor-dependent phagocytosis without inducing NF-kB-mediated inflammatory responses or reactive gliosis. Furthermore, alpha A beta-Gas6 can induce synergistic clearance of A beta by activating both microglial and astrocytic phagocytosis, resulting in better behavioral outcomes with substantially reduced synapse elimination and microhemorrhage in AD and cerebral amyloid angiopathy model mice compared with A beta antibody treatment. Our results suggest that alpha A beta-Gas6 could be a novel immunotherapeutic agent for AD that overcomes the side effects of conventional antibody therapy. | - |
dc.language | English | - |
dc.publisher | NATURE PORTFOLIO | - |
dc.title | Anti-inflammatory clearance of amyloid-beta by a chimeric Gas6 fusion protein | - |
dc.type | Article | - |
dc.identifier.wosid | 000836112500001 | - |
dc.identifier.scopusid | 2-s2.0-85135574586 | - |
dc.type.rims | ART | - |
dc.citation.volume | 28 | - |
dc.citation.issue | 9 | - |
dc.citation.beginningpage | 1802 | - |
dc.citation.endingpage | 1812 | - |
dc.citation.publicationname | NATURE MEDICINE | - |
dc.identifier.doi | 10.1038/s41591-022-01926-9 | - |
dc.contributor.localauthor | Chung, Won-Suk | - |
dc.contributor.localauthor | Kim, Chan Hyuk | - |
dc.contributor.nonIdAuthor | Kim, Minjin | - |
dc.contributor.nonIdAuthor | Lee, Yujean | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | TAU-MEDIATED NEURODEGENERATION | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | PHAGOCYTOSIS | - |
dc.subject.keywordPlus | RECEPTORS | - |
dc.subject.keywordPlus | MYELINOGENESIS | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | MODULATION | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.