Identification of a Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitor, BIP-135, That Prolongs the Median Survival Time of Δ7 SMA KO Mouse Model of Spinal Muscular Atrophy
View/ Open
21042770.pdf (2.234Mb)
Access Status
Full text of the requested work is not available in DASH at this time ("dark deposit"). For more information on dark deposits, see our FAQ.Author
Chen, Po C.
Gaisina, Irina N.
El-Khodor, Bassem F.
Ramboz, Sylvie
Kozikowski, Alan P.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1021/nl402052vMetadata
Show full item recordCitation
Lu, Bo, David P. Hoogerheide, Qing Zhao, Hengbin Zhang, Zhipeng Tang, Dapeng Yu, and Jene A. Golovchenko. 2013. “Pressure-Controlled Motion of Single Polymers through Solid-State Nanopores.” Nano Letters 13 (7) (July 10): 3048–3052. doi:10.1021/nl402052v.Abstract
The discovery of upregulated glycogen synthase kinase-3 (GSK-3) in various pathological conditions has led to the development of a host of chemically diverse small molecule GSK-3 inhibitors, such as BIP-135. GSK-3 inhibition emerged as an alternative therapeutic target for treating spinal muscular atrophy (SMA) when a number of GSK-3 inhibitors were shown to elevate survival motor neuron (SMN) levels in vitro and to rescue motor neurons when their intrinsic SMN level was diminished by SMN-specific short hairpin RNA (shRNA). Despite their cellular potency, the in vivo efficacy of GSK-3 inhibitors has yet to be evaluated in an animal model of SMA. Herein, we disclose that a potent and reasonably selective GSK-3 inhibitor, namely BIP-135, was tested in a transgenic Δ7 SMA KO mouse model of SMA and found to prolong the median survival of these animals. In addition, this compound was shown to elevate the SMN protein level in SMA patient-derived fibroblast cells as determined by Western blot, and was neuroprotective in a cell-based, SMA-related model of oxidative stress-induced neurodegeneration.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279955/Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:33373176
Collections
- FAS Scholarly Articles [17582]
Contact administrator regarding this item (to report mistakes or request changes)
Comments made during the workflow steps
FAR 2012 Rubin emailed 2017-03-10 MM meta.dark