Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer ' s Disease
DC Field | Value | Language |
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dc.contributor.author | Son, Seung Hwan | - |
dc.contributor.author | Lee, Na-Rae | - |
dc.contributor.author | Gee, Min Sung | - |
dc.contributor.author | Song, Chae Won | - |
dc.contributor.author | Lee, Soo Jin | - |
dc.contributor.author | Lee, Sang-Kyung | - |
dc.contributor.author | Lee, Yoonji | - |
dc.contributor.author | Kim, Hee Jin | - |
dc.contributor.author | Lee, Jong Kil | - |
dc.contributor.author | Inn, Kyung-Soo | - |
dc.contributor.author | Kim, Nam-Jung | - |
dc.date.accessioned | 2023-05-03T09:47:42Z | - |
dc.date.available | 2023-05-03T09:47:42Z | - |
dc.date.created | 2023-04-06 | - |
dc.date.issued | 2023-03 | - |
dc.identifier.issn | 2374-7943 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/184897 | - |
dc.description.abstract | Targeted protein degradation (TPD) provides unique advantages over gene knockdown in that it can induce selective degradation of disease-associated proteins attributed to pathological mutations or aberrant post-translational modifications (PTMs). Herein, we report a protein degrader, PRZ-18002, that selectively binds to an active form of p38 MAPK. PRZ-18002 induces degradation of phosphorylated p38 MAPK (p-p38) and a phosphomimetic mutant of p38 MAPK in a proteasome-depend-ent manner. Given that the activation of p38 MAPK plays pivotal roles in the pathophysiology of Alzheimer's disease (AD), selective degradation of p-p38 may provide an attractive therapeutic option for the treatment of AD. In the 5xFAD transgenic mice model of AD, intranasal treatment of PRZ-18002 reduces p-p38 levels and alleviates microglia activation and amyloid beta (A beta) deposition, leading to subsequent improvement of spatial learning and memory. Collectively, our findings suggest that PRZ-18002 ameliorates AD pathophysiology via selective degradation of p-p38, highlighting a novel therapeutic TPD modality that targets a specific PTM to induce selective degradation of neurodegenerative disease-associated protein. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer ' s Disease | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Sang-Kyung | - |
dc.identifier.doi | 10.1021/acscentsci.2c01369 | - |
dc.identifier.scopusid | 2-s2.0-85149479862 | - |
dc.identifier.wosid | 000942865600001 | - |
dc.identifier.bibliographicCitation | ACS CENTRAL SCIENCE, v.9, no.3, pp.417 - 426 | - |
dc.relation.isPartOf | ACS CENTRAL SCIENCE | - |
dc.citation.title | ACS CENTRAL SCIENCE | - |
dc.citation.volume | 9 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 417 | - |
dc.citation.endPage | 426 | - |
dc.type.rims | ART | - |
dc.type.docType | Article; Early Access | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | SYNAPTIC DYSFUNCTION | - |
dc.subject.keywordPlus | TAU-PROTEIN | - |
dc.subject.keywordPlus | P38-ALPHA | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordPlus | BETA | - |
dc.identifier.url | https://pubs.acs.org/doi/10.1021/acscentsci.2c01369 | - |
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