Phosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy. From this point of view, PDE inhibition will provide a promising therapeutic strategy for treating neurodegenerative disorders. Herein, we summarized the PDE inhibitors that have entered the clinical trials or been discovered in recent five years. Well-designed clinical or preclinical investigations have confirmed the effectiveness of PDE inhibitors, such as decreasing Aβ oligomerization and tau phosphorylation, alleviating neuro-inflammation and oxidative stress, modulating neuronal plasticity and improving long-term cognitive impairment.

中文翻译：

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小分子磷酸二酯酶抑制剂在神经退行性疾病中的机遇与展望

磷酸二酯酶 (PDE) 是一个酶超家族，负责两个第二信使的水解：环单磷酸腺苷 (cAMP) 和环单磷酸鸟苷 (cGMP)。 PDE 抑制通过激活 cAMP 反应元件结合蛋白 (CREB) 促进基因转录，启动脑源性神经营养因子 (BDNF) 的基因转录。该程序发挥神经保护作用以及运动和认知改善功效。从这个角度来看，PDE抑制将为治疗神经退行性疾病提供一种有前景的治疗策略。在此，我们总结了近五年来已进入临床试验或发现的PDE抑制剂。精心设计的临床或临床前研究已经证实了 PDE 抑制剂的有效性，例如减少 Aβ 寡聚化和 tau 磷酸化、减轻神经炎症和氧化应激、调节神经元可塑性和改善长期认知障碍。