Small molecule, non-peptide p75NTR ligands inhibit A$β$-induced neurodegeneration and synaptic impairment. Yang, T, Knowles, K, J, Lu, Q, Zhang, H, Arancio, O, Moore, A, L, Chang, T, Wang, Q, Andreasson, K, Rajadas, J, Fuller, G, G, Xie, Y, Massa, M, S, Longo, & M, F PLoS ONE, 2008.
Small molecule, non-peptide p75NTR ligands inhibit A$β$-induced neurodegeneration and synaptic impairment [link]Paper  abstract   bibtex   
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 A$β$-induced degeneration and synaptic dysfunction. These ligands inhibited A$β$-induced neuritic dystrophy, death of cultured neurons and A$β$-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited A$β$-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3$β$ and c-Jun, and tau phosphorylation, and prevented A$β$-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked A$β$-induced hippocampal LTP impairment. These studies support an extensive intersection between p75NTR signaling and A$β$ 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 A$β$-induced neuronal dystrophy and death.
@article{ Yang:2008un,
  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 A$β$-induced degeneration and synaptic dysfunction. These ligands inhibited A$β$-induced neuritic dystrophy, death of cultured neurons and A$β$-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited A$β$-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3$β$ and c-Jun, and tau phosphorylation, and prevented A$β$-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked A$β$-induced hippocampal LTP impairment. These studies support an extensive intersection between p75NTR signaling and A$β$ 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 A$β$-induced neuronal dystrophy and death.},
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  author = {Yang, T and Knowles, J K and Lu, Q and Zhang, H and Arancio, O and Moore, L A and Chang, T and Wang, Q and Andreasson, K and Rajadas, J and Fuller, G G and Xie, Y and Massa, S M and Longo, F M},
  journal = {PLoS ONE},
  number = {11},
  title = {{Small molecule, non-peptide p75NTR ligands inhibit A$β$-induced neurodegeneration and synaptic impairment}},
  url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-56149091270\&partnerID=40\&md5=02b623f6b9db868ddf40a767f45365dd},
  volume = {3},
  year = {2008}
}

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