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    Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment

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    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
    URI
    http://hdl.handle.net/10342/3430
    Subject
     Alzheimer's disease; P75 neurotrophin receptor; Small molecule ligands 
    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. , (. Retrieved from http://hdl.handle.net/10342/3430

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    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". . . (.), November 2008. February 28, 2021. 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,"  , no. (November 2008), http://hdl.handle.net/10342/3430 (accessed February 28, 2021).
    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. . November 2008; () . http://hdl.handle.net/10342/3430. Accessed February 28, 2021.
    Collections
    • Pharmacology and Toxicology
    Publisher
    East Carolina University

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