Amelioration of neurodegenerative diseases by cell death-induced cytoplasmic delivery of humanin
DC Field | Value | Language |
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dc.contributor.author | Park, Tae-Yoon | - |
dc.contributor.author | Kim, Seung-Hyung | - |
dc.contributor.author | Shin, Yoon-Chul | - |
dc.contributor.author | Lee, Nae-Hyun | - |
dc.contributor.author | Lee, Rae-Kyung Christina | - |
dc.contributor.author | Shim, Jae-Hyuck | - |
dc.contributor.author | Glimcher, Laurie H. | - |
dc.contributor.author | Mook-Jung, Inhee | - |
dc.contributor.author | Cheong, Eunji | - |
dc.contributor.author | Kim, Won-Ki | - |
dc.contributor.author | Honda, Fumiko | - |
dc.contributor.author | Morio, Tomohiro | - |
dc.contributor.author | Lim, Jong-Soon | - |
dc.contributor.author | Lee, Sang-Kyou | - |
dc.date.accessioned | 2021-09-06T03:21:23Z | - |
dc.date.available | 2021-09-06T03:21:23Z | - |
dc.date.created | 2021-06-14 | - |
dc.date.issued | 2013-03-28 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/103709 | - |
dc.description.abstract | Inhibition of the early intracellular event that triggers neurodegenerative cascades and reversal of neuronal cell death are essential for effective treatment of Alzheimer's disease (AD). In this study, a novel therapeutic for AD, a transducible humanin with an extended caspase-3 cleavage sequence (tHN-C3), was developed and showed multiple mechanisms of therapeutic action. These included targeted delivery of anti-apoptotic protein humanin through the blood-brain barrier (BBB) to neuronal cells, specific inhibition of caspase-3 activation to inhibit the early triggering of AD progression, and delivery of humanin into the cytoplasm of neuronal cells undergoing apoptosis where it exerts its anti-apoptotic functions effectively. The tHN-C3 prevented neuronal cell death induced by H2O2, or soluble A beta(42), via Bax binding. In animal models of AD induced by amyloid beta, in Tg2576 mice, and in the rat middle cerebral artery occlusion model of stroke, tHN-C3 effectively prevented neuronal cell death, inflammatory cell infiltration into the brain, and improved cognitive memory. The therapeutic effectiveness of tHN-C3 was comparable to that of Aricept, a clinically approved drug for AD treatment. Therefore, tHN-C3 may be a new remedy with multiple therapeutic functions targeting the early and late stages of neurodegeneration in AD and other brain injuries. (C) 2013 Elsevier B. V. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.subject | TG2576 MOUSE MODEL | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | A-BETA | - |
dc.subject | PROTEIN TRANSDUCTION | - |
dc.subject | AMYLOID DEPOSITION | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | MEMORY DEFICITS | - |
dc.subject | APOPTOSIS | - |
dc.subject | BAX | - |
dc.subject | ACTIVATION | - |
dc.title | Amelioration of neurodegenerative diseases by cell death-induced cytoplasmic delivery of humanin | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Won-Ki | - |
dc.identifier.doi | 10.1016/j.jconrel.2012.12.022 | - |
dc.identifier.scopusid | 2-s2.0-84873739212 | - |
dc.identifier.wosid | 000316676900013 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CONTROLLED RELEASE, v.166, no.3, pp.307 - 315 | - |
dc.relation.isPartOf | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.title | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.volume | 166 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 307 | - |
dc.citation.endPage | 315 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | TG2576 MOUSE MODEL | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | PROTEIN TRANSDUCTION | - |
dc.subject.keywordPlus | AMYLOID DEPOSITION | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | MEMORY DEFICITS | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | BAX | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordAuthor | Alzheimer | - |
dc.subject.keywordAuthor | Drug delivery | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Inflammation | - |
dc.subject.keywordAuthor | Neuroprotection | - |
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