García Ana M, Salado Irene G, Perez Daniel I, Brea José, Morales-García Jose A, González-García Alejandro, Cadavid María Isabel, Loza María Isabel, Luque Francisco Javier, Perez-Castillo Ana, Martinez Ana, Gil Carmen
Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain.
Instituto de Farmacia Industrial, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain.
Future Med Chem. 2017 May;9(8):731-748. doi: 10.4155/fmc-2017-0005. Epub 2017 May 9.
Since neuroinflammation is partially mediated by cAMP levels and PDE10A enzyme is able to regulate these levels being highly expressed in striatum, its inhibitors emerged as useful drugs to mitigate this inflammatory process and hence the neuronal death associated with Parkinson's disease (PD). Methodology & results: To study the utility of PDE10A as a pharmacological target for PD, in this work we propose the search and development of new PDE10A inhibitors that could be useful as pharmacological tools in models of the disease and presumably as potential drug candidates. By using different medicinal chemistry approaches we have discovered imidazole-like PDE10A inhibitors and showed their neuroprotective actions.
Here, we demonstrate the neuroprotective effect of PDE10A inhibitors in cellular models of PD. [Formula: see text].
由于神经炎症部分由环磷酸腺苷（cAMP）水平介导，且磷酸二酯酶10A（PDE10A）酶能够调节这些水平，在纹状体中高表达，其抑制剂成为减轻这种炎症过程以及与帕金森病（PD）相关的神经元死亡的有用药物。方法与结果：为研究PDE10A作为PD的药理学靶点的效用，在本研究中，我们提议寻找和开发新的PDE10A抑制剂，这些抑制剂可作为该疾病模型中的药理学工具，并可能作为潜在的候选药物。通过使用不同的药物化学方法，我们发现了咪唑样PDE10A抑制剂并展示了它们的神经保护作用。
在此，我们证明了PDE10A抑制剂在PD细胞模型中的神经保护作用。[公式：见正文]
