Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Kim, Hyeon Jeong | - |
dc.contributor.author | Kim, Haelee | - |
dc.contributor.author | Song, Jaeyoung | - |
dc.contributor.author | Hong, Jun Young | - |
dc.contributor.author | Lee, Elijah Hwejin | - |
dc.contributor.author | Londhe, Ashwini M | - |
dc.contributor.author | Choi, Ji Won | - |
dc.contributor.author | Park, Sun Jun | - |
dc.contributor.author | Oh, Eunseok | - |
dc.contributor.author | Yoon, Heeseok | - |
dc.contributor.author | Hwang, Hoosang | - |
dc.contributor.author | Hahn, Dongyup | - |
dc.contributor.author | Jung, Kyungjin | - |
dc.contributor.author | Kwon, Sugyeong | - |
dc.contributor.author | Kadayat, Tara Man | - |
dc.contributor.author | Ma, Min Jung | - |
dc.contributor.author | Joo, Jeongmin | - |
dc.contributor.author | Kim, Jina | - |
dc.contributor.author | Bae, Jae Hyun | - |
dc.contributor.author | Hwang, Hayoung | - |
dc.contributor.author | Pae, Ae Nim | - |
dc.contributor.author | Cho, Sung Jin | - |
dc.contributor.author | Park, Jong Hyun | - |
dc.contributor.author | Chin, Jungwook | - |
dc.contributor.author | Kang, Heonjoong | - |
dc.contributor.author | Park, Ki Duk | - |
dc.date.accessioned | 2024-11-07T02:30:27Z | - |
dc.date.available | 2024-11-07T02:30:27Z | - |
dc.date.created | 2024-11-06 | - |
dc.date.issued | 2024-09 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://pubs.kist.re.kr/handle/201004/151005 | - |
dc.description.abstract | Rationale: Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by neurotoxicity, excessive inflammation, and cognitive impairment. The peroxisome proliferator-activated receptor (PPAR) δ is a potential target for AD. However, its regulatory mechanisms and therapeutic potential in AD remain unclear. We aimed to investigate if the activation of PPARδ using a highly selective and potent agonist could provide an effective therapeutic strategy against AD. Methods: We synthesized a novel PPARδ agonist, 5a, containing a selenazole group and determined the X-ray crystal structure of its complex with PPARδ. The drug-like properties of 5a were assessed by analyzing cytochrome P450 (CYP) inhibition, microsomal stability, pharmacokinetics, and mutagenicity. We investigated the anti-inflammatory effects of 5a using lipopolysaccharide (LPS)-stimulated BV-2 microglia and neuroinflammatory mouse model. The therapeutic efficacy of 5a was evaluated in AD mice with scopolamine-induced memory impairment and APP/PS1 by analyzing cognitive function, glial reactivity, and amyloid pathology. Results: Compound 5a, the most potent and selective PPARδ agonist, was confirmed to bind hPPARδ in a complex by X-ray crystallographic analysis. PPARδ activation using 5a showed potent anti-inflammatory effects in activated glial cells and mouse model of neuroinflammation. Administration of 5a inhibited amyloid plaque deposition by suppressing the expression of neuronal beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), and reduced abnormal glial hyperactivation and inflammatory responses, resulting in improved learning and memory in the APP/PS1 mouse model of AD. Conclusion: We identified that specific activation of PPARδ provides therapeutic effects on multiple pathogenic phenotypes of AD, including neuroinflammation and amyloid deposition. Our findings suggest the potential of PPARδ as a promising drug target for treating AD. | - |
dc.language | English | - |
dc.publisher | Ivyspring International Publisher | - |
dc.title | Highly potent and selective PPARδ agonist reverses memory deficits in mouse models of Alzheimer's disease | - |
dc.type | Article | - |
dc.identifier.doi | 10.7150/thno.96707 | - |
dc.description.journalClass | 1 | - |
dc.identifier.bibliographicCitation | Theranostics, v.14, no.16, pp.6088 - 6108 | - |
dc.citation.title | Theranostics | - |
dc.citation.volume | 14 | - |
dc.citation.number | 16 | - |
dc.citation.startPage | 6088 | - |
dc.citation.endPage | 6108 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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