Neuroprotection in the PNS: erythropoietin and immunophilin ligands.
Neuroprotection in the PNS: erythropoietin and immunophilin ligands.
复制标题
PNS 中的神经保护：促红细胞生成素和亲免素配体。
DOI：
10.1111/j.1749-6632.2005.tb00059.x
复制
发表时间：
2005
影响因子：
5.2
通讯作者：
Keswani,SanjayC
中科院分区：
文献类型：
--
作者：
Höke,Ahmet;Keswani,SanjayC
摘要：许多影响周围神经系统（PNS）的疾病导致远端轴突变性，而不是神经元细胞体的丧失。旨在促进受损神经元存活（即防止细胞死亡）的策略可能不适用于许多PNS疾病。我们已经建立了体外和体内动物模型来研究获得性周围神经病变的机制，并利用这些模型来评估新化合物的治疗潜力。近年来，促红细胞生成素（EPO）被认为是中枢神经系统中一种新型的神经保护剂。在PNS中，我们最近发现雪旺细胞来源的EPO作为一种内源性神经保护剂，在周围神经病变模型中最有效地预防远端轴突变性。同样，我们发现亲免疫蛋白配体在PNS中也具有神经保护作用，可以防止周围神经病变模型中的轴突变性。EPO和非免疫抑制性亲免疫素配体都处于治疗获得性周围神经病变的早期临床开发阶段。
Abstract:Many illnesses that affect the peripheral nervous system (PNS) lead to distal axonal degeneration rather than loss of neuronal cell bodies. Strategies aimed at promoting survival of injured neurons (i.e., preventing cell death) may not be applicable to many PNS illnesses. We have developedin vitroandin vivoanimal models to study mechanisms of acquired peripheral neuropathies and used these models to evaluate the therapeutic potential of novel compounds. In recent years, erythropoietin (EPO) has been recognized as a novel neuroprotectant in the central nervous system. In the PNS, we recently showed that Schwann cell‐derived EPO acts as an endogenous neuroprotectant and that it is most effective in preventing distal axonal degeneration seen in models of peripheral neuropathy. Similarly, we showed that immunophilin ligands are also neuroprotective in the PNS and prevent axonal degeneration seen in models of peripheral neuropathies. Both EPO and non‐immunosuppressive immunophilin ligands are in early clinical development for the treatment of acquired peripheral neuropathies.