Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms.

Abstract

A number of factors limit the therapeutic application of neurotrophin proteins, such as nerve growth factor (NGF) and brain-derived growth factor (BDNF), for Alzheimer's and other neurodegenerative diseases. These factors include unfavorable pharmacological properties typical of proteins and the pleiotropic effects mediated by protein-ligand interactions with p75(NTR), Trk, and sortilin neurotrophin receptors. Targeted modulation of p75(NTR) provides a strategy for preventing degeneration without promoting TrkA-mediated deleterious effects, and targeted activation of TrkB might achieve more favorable neurotrophic effects than those achieved by concomitant activation of p75(NTR) and TrkB. The discovery of small molecules functioning as ligands at specific neurotrophin receptors has made possible for the first time approaches for modulating selected components of neurotrophin signaling processes for the purpose of modulating underlying Alzheimer's disease mechanisms.

• Authors: Frank M Longo, Tao Yang, Juliet K Knowles, Youmei Xie, Laura A Moore, Stephen M Massa
• Journal: Current Alzheimer research (Curr Alzheimer Res) Vol. 4 Issue 5 Pg. 503-6 (Dec 2007) ISSN: 1567-2050 [Print] United Arab Emirates
• PMID: 18220511 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)

Chemical References

• Ligands
• Neuroprotective Agents
• Receptors, Nerve Growth Factor

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Animals
• Humans
• Ligands
• Neuroprotective Agents (therapeutic use)
• Receptors, Nerve Growth Factor (drug effects, therapeutic use)