Longo Frank M, Yang Tao, Knowles Juliet K, Xie Youmei, Moore Laura A, Massa Stephen M
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Curr Alzheimer Res. 2007 Dec;4(5):503-6. doi: 10.2174/156720507783018316.
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.
许多因素限制了神经营养蛋白（如神经生长因子（NGF）和脑源性生长因子（BDNF））在阿尔茨海默病和其他神经退行性疾病中的治疗应用。这些因素包括蛋白质典型的不良药理学特性以及蛋白质与p75（NTR）、Trk和sortilin神经营养素受体相互作用介导的多效性效应。对p75（NTR）进行靶向调节提供了一种在不促进TrkA介导的有害效应的情况下预防神经退行性变的策略，而对TrkB进行靶向激活可能比同时激活p75（NTR）和TrkB产生更有利的神经营养作用。作为特定神经营养素受体配体的小分子的发现，首次使得为调节阿尔茨海默病潜在机制而调节神经营养素信号传导过程的选定成分成为可能。
