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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Katrin Andreasson (Creator)

Ottavio Arancio (Creator)

Timothy Chang (Creator)

Gerald G. Fuller (Creator)

Juliet K. Knowles (Creator)

Frank M. Longo (Creator)

Qun Lu (Creator)

Stephen M. Massa (Creator)

Laura A. Moore (Creator)

Jayakumar Rajadas (Creator)

Qian Wang (Creator)

Youmei Xie (Creator)

Tao Yang (Creator)

Hong Zhang (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: The p75 neurotrophin receptor (p75NTR) is expressed by neurons particularly vulnerable in Alzheimer’s disease (AD). We tested\r\nthe hypothesis that non-peptide, small molecule p75NTR ligands found to promote survival signaling might prevent Abinduced\r\ndegeneration and synaptic dysfunction. These ligands inhibited Ab-induced neuritic dystrophy, death of cultured\r\nneurons and Ab-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Ab-induced\r\nactivation of molecules involved in AD pathology including calpain/cdk5, GSK3b and c-Jun, and tau phosphorylation, and\r\nprevented Ab-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked Ab-induced hippocampal LTP\r\nimpairment. These studies support an extensive intersection between p75NTR signaling and Ab pathogenic mechanisms, and\r\nintroduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling\r\npathways, reverse synaptic impairment and inhibit Ab-induced neuronal dystrophy and death. Originally published PLoS ONE, Vol. 3, No. 11, Nov 2008

Additional Information

Publication

Other

PLoS ONE\; 3:11 p. e3604

Language: English

Date: 2023

Subjects

Alzheimer's disease;P75 neurotrophin receptor;Small molecule ligands

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