ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated.
If you have any questions, please contact Marianne Reed at mreed@ku.edu .
Identification of Human ABAD Inhibitors for Rescuing Aβ-Mediated Mitochondrial Dysfunction
dc.contributor.author | Valasani, Koteswara Rao | |
dc.contributor.author | Sun, Qinru | |
dc.contributor.author | Hu, Gang | |
dc.contributor.author | Li, Jianping | |
dc.contributor.author | Du, Fang | |
dc.contributor.author | Guo, Yaopeng | |
dc.contributor.author | Carlson, Emily A. | |
dc.contributor.author | Gan, Xueqi | |
dc.contributor.author | Yan, Shirley ShiDu | |
dc.date.accessioned | 2017-02-27T22:18:50Z | |
dc.date.available | 2017-02-27T22:18:50Z | |
dc.date.issued | 2014-07-06 | |
dc.identifier.citation | Valaasani, Koteswara, Qinru Sun, Gang Hu, Jianping Li, Fang Du, Yaopeng Guo, Emily Carlson, Xueqi Gan, and Shirley Yan. "Identification of Human ABAD Inhibitors for Rescuing Aβ-Mediated Mitochondrial Dysfunction." Current Alzheimer Research 11.2 (2014): 128-36. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23278 | |
dc.description.abstract | Amyloid beta (Aβ) binding alcohol dehydrogenase (ABAD) is a cellular cofactor for promoting (Aβ)-mediated mitochondrial and neuronal dysfunction, and cognitive decline in transgenic Alzheimer's disease (AD) mouse models. Targeting mitochondrial ABAD may represent a novel therapeutic strategy against AD. Here, we report the biological activity of small molecule ABAD inhibitors. Using in vitro surface plasmon resonance (SPR) studies, we synthesized compounds with strong binding affinities for ABAD. Further, these ABAD inhibitors (ABAD-4a and 4b) reduced ABAD enzyme activity and administration of phosphonate derivatives of ABAD inhibitors antagonized calcium-mediated mitochondrial swelling. Importantly, these compounds also abolished Aβ-induced mitochondrial dysfunction as shown by increased cytochrome c oxidase and adenosine-5′-triphosphate levels, suggesting protective mitochondrial function effects of these synthesized compounds. Thus, these compounds are potential candidates for further pharmacologic development to target ABAD to improve mitochondrial function. | en_US |
dc.publisher | Bentham Science Publishers | en_US |
dc.subject | ABAD inhibitors | en_US |
dc.subject | Adenosine-5'-triphosphate | en_US |
dc.subject | Amyloid beta | en_US |
dc.subject | Benzothiazole amino phosphonates | en_US |
dc.subject | Cytochrome c oxidase | en_US |
dc.subject | Mitochondrial dysfunction | en_US |
dc.title | Identification of Human ABAD Inhibitors for Rescuing Aβ-Mediated Mitochondrial Dysfunction | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Yan, Shirley Shidu | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.2174/1567205011666140130150108 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
Files in this item
This item appears in the following Collection(s)
-
Pharmacy Scholarly Works [299]