Small Molecule Neurotrophin Receptor Ligands: Novel Strategies for Targeting Alzheimers Disease Mechanisms

Author(s): Frank M. Longo, Tao Yang, Juliet K. Knowles, Youmei Xie, Laura A. Moore, Stephen M. Massa.

Journal Name: Current Alzheimer Research

Volume 4 , Issue 5 , 2007

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A number of factors limit the therapeutic application of neurotrophin proteins, such as nerve growth factor (NGF) and brain-derived growth factor (BDNF), for Alzheimers and other neurodegenerative diseases. These factors include unfavorable pharmacological properties typical of proteins and the pleiotropic effects mediated by protein-ligand interactions with p75NTR, Trk, and sortilin neurotrophin receptors. Targeted modulation of p75NTR 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 p75NTR 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 Alzheimers disease mechanisms.

Keywords: TrkA interaction, AKT signaling, BDNF polymorphism, neurotrophic effect, NGF promotion

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Article Details

Year: 2007
Page: [503 - 506]
Pages: 4
DOI: 10.2174/156720507783018316
Price: $58

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