磷酸二酯酶及其抑制剂在神经退行性疾病中的研究进展

Research progress in phosphodiesterases and their inhibitors in neurodegenerative diseases

磷酸二酯酶(PDE)是第二信使环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)的特异性水解酶,对细胞内环核苷酸信号具有重要的调控作用。由于cAMP和cGMP信号与神经元的发生、存活、信息传递及突触可塑性等密切相关,PDE现已成为包括神经退行性疾病在内的多个疾病的重要靶点。在阿尔茨海默病、亨廷顿病和帕金森病等常见神经退行性疾病的临床前研究中,已有多个PDE选择性抑制剂被证实具有神经元保护作用,有的甚至已进入了临床研究阶段。本文就常见神经退行性疾病中PDE及其抑制剂的研究进展作一简要综述。

Phosphodiesterases(PDEs)are responsible for the breakdown of cyclic nucleotides,cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP).They are crucia regulators of cyclic nucleotide-mediated signaling.Since cAMP and cGMP signalings are associated with neurogenesis,neuronal survival,neurotransmission and neuroplasticity,PDEs have become a vita target for treatment in a wide array of disorders,including neurodegenerative diseases.Furthermore,various PDE inhibitors have been reported pre-clinicaly and even clinicaly to be neuroprotective in Alzheimer disease,Huntington disease,Parkinson disease and other neurodegenerative disorders.In this review,we discuss the research progress in PDEs and their inhibitors in common neurodegenerative diseases.