Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment
Author
Yang, Tao; Knowles, Juliet K.; Lu, Qun; Zhang, Hong; Arancio, Ottavio; Moore, Laura A.; Chang, Timothy; Wang, Qian; Andreasson, Katrin; Rajadas, Jayakumar; Fuller, Gerald G.; Xie, Youmei; Massa, Stephen M.; Longo, Frank M.
Abstract
The p75 neurotrophin receptor (p75NTR) is expressed by neurons particularly vulnerable in Alzheimer’s disease (AD). We tested
the hypothesis that non-peptide, small molecule p75NTR ligands found to promote survival signaling might prevent Abinduced
degeneration and synaptic dysfunction. These ligands inhibited Ab-induced neuritic dystrophy, death of cultured
neurons and Ab-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Ab-induced
activation of molecules involved in AD pathology including calpain/cdk5, GSK3b and c-Jun, and tau phosphorylation, and
prevented Ab-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked Ab-induced hippocampal LTP
impairment. These studies support an extensive intersection between p75NTR signaling and Ab pathogenic mechanisms, and
introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling
pathways, reverse synaptic impairment and inhibit Ab-induced neuronal dystrophy and death. Originally published PLoS ONE, Vol. 3, No. 11, Nov 2008
Date
2008-11-03
Citation:
APA:
Yang, Tao, & Knowles, Juliet K., & Lu, Qun, & Zhang, Hong, & Arancio, Ottavio, & Moore, Laura A., & Chang, Timothy, & Wang, Qian, & Andreasson, Katrin, & Rajadas, Jayakumar, & Fuller, Gerald G., & Xie, Youmei, & Massa, Stephen M., & Longo, Frank M.. (November 2008).
Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment.
PLoS ONE,
3(11),
-
. Retrieved from
http://hdl.handle.net/10342/3430
MLA:
Yang, Tao, and Knowles, Juliet K., and Lu, Qun, and Zhang, Hong, and Arancio, Ottavio, and Moore, Laura A., and Chang, Timothy, and Wang, Qian, and Andreasson, Katrin, and Rajadas, Jayakumar, and Fuller, Gerald G., and Xie, Youmei, and Massa, Stephen M., and Longo, Frank M..
"Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment". PLoS ONE.
3:11. (e3604),
November 2008.
September 27, 2023.
http://hdl.handle.net/10342/3430.
Chicago:
Yang, Tao and Knowles, Juliet K. and Lu, Qun and Zhang, Hong and Arancio, Ottavio and Moore, Laura A. and Chang, Timothy and Wang, Qian and Andreasson, Katrin and Rajadas, Jayakumar and Fuller, Gerald G. and Xie, Youmei and Massa, Stephen M. and Longo, Frank M.,
"Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment," PLoS ONE 3, no.
11 (November 2008),
http://hdl.handle.net/10342/3430 (accessed
September 27, 2023).
AMA:
Yang, Tao, Knowles, Juliet K., Lu, Qun, Zhang, Hong, Arancio, Ottavio, Moore, Laura A., Chang, Timothy, Wang, Qian, Andreasson, Katrin, Rajadas, Jayakumar, Fuller, Gerald G., Xie, Youmei, Massa, Stephen M., Longo, Frank M..
Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment. PLoS ONE.
November 2008;
3(11):
e3604.
http://hdl.handle.net/10342/3430. Accessed
September 27, 2023.
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Publisher
East Carolina University