Amelioration of neurodegenerative diseases by cell death-induced cytoplasmic delivery of humanin
- Authors
- Park, Tae-Yoon; Kim, Seung-Hyung; Shin, Yoon-Chul; Lee, Nae-Hyun; Lee, Rae-Kyung Christina; Shim, Jae-Hyuck; Glimcher, Laurie H.; Mook-Jung, Inhee; Cheong, Eunji; Kim, Won-Ki; Honda, Fumiko; Morio, Tomohiro; Lim, Jong-Soon; Lee, Sang-Kyou
- Issue Date
- 28-3월-2013
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Alzheimer; Drug delivery; Apoptosis; Inflammation; Neuroprotection
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.166, no.3, pp.307 - 315
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 166
- Number
- 3
- Start Page
- 307
- End Page
- 315
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/103709
- DOI
- 10.1016/j.jconrel.2012.12.022
- ISSN
- 0168-3659
- 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.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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