Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer's disease mice
DC Field | Value | Language |
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dc.contributor.author | Park, Min Hee | - |
dc.contributor.author | Park, Kang Ho | - |
dc.contributor.author | Choi, Byung Jo | - |
dc.contributor.author | Han, Wan Hui | - |
dc.contributor.author | Yoon, Hee Ji | - |
dc.contributor.author | Jung, Hye Yoon | - |
dc.contributor.author | Lee, Jihoon | - |
dc.contributor.author | Song, Im-Sook | - |
dc.contributor.author | Lim, Dong Yu | - |
dc.contributor.author | Choi, Min-Koo | - |
dc.contributor.author | Yang-Ha Lee | - |
dc.contributor.author | Park, Cheol-Min | - |
dc.contributor.author | Wang, Ming | - |
dc.contributor.author | Jo, Jihoon | - |
dc.contributor.author | Kim, Hee-Jin | - |
dc.contributor.author | Kim, Seung Hyun | - |
dc.contributor.author | Schuchman, Edward H. | - |
dc.contributor.author | Jin, Hee Kyung | - |
dc.contributor.author | Bae, Jae-Sung | - |
dc.date.accessioned | 2022-07-06T10:36:22Z | - |
dc.date.available | 2022-07-06T10:36:22Z | - |
dc.date.created | 2022-03-07 | - |
dc.date.issued | 2022-01 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/139755 | - |
dc.description.abstract | Alzheimer's disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.title | Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer's disease mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Hee-Jin | - |
dc.contributor.affiliatedAuthor | Kim, Seung Hyun | - |
dc.identifier.doi | 10.1073/pnas.2115082119 | - |
dc.identifier.scopusid | 2-s2.0-85123067389 | - |
dc.identifier.wosid | 000748778000014 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.119, no.3, pp.1 - 12 | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.title | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.volume | 119 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 12 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | TRANSGENIC MOUSE MODEL | - |
dc.subject.keywordPlus | ACID SPHINGOMYELINASE | - |
dc.subject.keywordPlus | GHRELIN | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | NEUROGENESIS | - |
dc.subject.keywordPlus | TRANSLATION | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.subject.keywordPlus | INNATE | - |
dc.subject.keywordPlus | ROLES | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | ASM direct inhibitor | - |
dc.subject.keywordAuthor | GHSR1 alpha agonist | - |
dc.subject.keywordAuthor | memory improvement | - |
dc.subject.keywordAuthor | small compound | - |
dc.identifier.url | https://www.pnas.org/doi/full/10.1073/pnas.2115082119 | - |
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