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 he hypothesis that non-peptide small molecule p75NTR ligands found to promote survival signaling might prevent Abinduced egeneration and synaptic dysfunction. These ligands inhibited Ab-induced neuritic dystrophy death of cultured eurons and Ab-induced death of pyramidal neurons in hippocampal slice cultures. Moreover ligands inhibited Ab-induced ctivation of molecules involved in AD pathology including calpain/cdk5 GSK3b and c-Jun and tau phosphorylation and revented Ab-induced inactivation of AKT and CREB. Finally a p75NTR ligand blocked Ab-induced hippocampal LTP mpairment. These studies support an extensive intersection between p75NTR signaling and Ab pathogenic mechanisms and ntroduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling athways 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(November 2008) p. e3604.

Language: English

Date: 2011

Keywords

Alzheimer's disease, p75 neurotrophin receptor, small molecule ligands

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