Universidad CEU San Pablo, Boadilla del Monte, Madrid, Spain.
Curr Med Chem. 2009;16(25):3322-9. doi: 10.2174/092986709788803240.
striatum of rodents in experimental models of Parkinson's disease. Interestingly, immunohistochemical studies have shown increased levels of PTN expression in the substantia nigra of patients with Parkinson's disease. Since, in other contexts, PTN has been shown to be critical in repair processes in the injured nervous system, the antecedents suggest that PTN could exhibit protective effects in Parkinson's disease. This hypothesis was confirmed when PTN was shown to support survival of dopaminergic neurons and to promote the differentiation of neural stem cells to dopaminergic neurons. These findings suggest a new therapeutic approach in the treatment of Parkinson's disease based on the molecular mechanism of action of PTN. Pleiotrophin receptor, receptor protein tyrosine phosphatase (RPTP) beta/zeta, is found active in monomeric form in neurons and glia within the central nervous system. Pleiotrophin induces dimerization of RPTPbeta/zeta inactivating its phosphatase activity, thus increasing the phosphorylation levels of its substrates such as beta-catenin, Fyn and beta-adducin. These substrates have been shown to be critical for the proliferation of dopaminergic progenitors and the survival and differentiation of dopaminergic neurons. This review summarizes the strong scientific basis to consider blocking RPTPbeta/zeta as a potentially novel therapeutic strategy in the treatment of Parkinson's disease and discusses various starting points to design antagonists of this receptor.
纹状体在帕金森病的实验模型中。有趣的是，免疫组织化学研究表明帕金森病患者黑质中 PTN 的表达水平增加。由于在其他情况下，PTN 已被证明在受损神经系统的修复过程中至关重要，因此这一前提表明 PTN 可能在帕金森病中表现出保护作用。当 PTN 被证明支持多巴胺能神经元的存活并促进神经干细胞向多巴胺能神经元的分化时，这一假设得到了证实。这些发现为基于 PTN 的分子作用机制治疗帕金森病提供了一种新的治疗方法。多效蛋白受体，受体蛋白酪氨酸磷酸酶（RPTP）β/ζ，在中枢神经系统内的神经元和神经胶质中以单体形式存在。多效蛋白诱导 RPTPβ/ζ 的二聚化，使其磷酸酶活性失活，从而增加其底物如β-连环蛋白、Fyn 和β-辅肌动蛋白的磷酸化水平。这些底物已被证明对多巴胺能前体细胞的增殖以及多巴胺能神经元的存活和分化至关重要。这篇综述总结了将阻断 RPTPβ/ζ 作为治疗帕金森病的一种潜在新的治疗策略的强有力的科学依据，并讨论了设计该受体拮抗剂的各种起点。
