Phosphodiesterase: an interface connecting cognitive deficits to neuropsychiatric and neurodegenerative diseases.
Phosphodiesterase: an interface connecting cognitive deficits to neuropsychiatric and neurodegenerative diseases.
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DOI：
10.2174/1381612820666140826115559
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发表时间：
2014-12
影响因子：
3.1
通讯作者：
Zhen-Zhen Wang-Zhen;Yi Zhang;Han-Ting Zhang;Yun‐feng Li
中科院分区：
文献类型：
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作者：
Zhen-Zhen Wang-Zhen;Yi Zhang;Han-Ting Zhang;Yun‐feng Li
磷酸二酯酶(PDE)是目前已知的唯一能降解细胞内cAMP和/或cGMP的酶。PDE超家族由11个家族(PDE1-PDE11)组成，每个家族有1-4个亚型。一些亚型可能有多个剪接变体(例如PDE4D1-PDE4D11)，导致到目前为止总共有100多个已知蛋白质。近年来，通过控制上述两种第二信使的水解率，PDE作为情绪障碍和/或影响认知活动的疾病的治疗靶点的潜力越来越受到关注。认知功能丧失是大多数中枢神经系统疾病患者面临的主要主诉之一，对日常生活质量的负面影响更加突出。认知功能障碍通常是患有神经精神疾病和神经退行性疾病的患者的预后，包括抑郁症、精神分裂症和阿尔茨海默病。这篇综述将集中在PDE在认知缺陷与神经精神和神经退行性疾病之间的接口上的贡献。这有望有助于理解和发现选择性PDE抑制剂具有治疗与神经精神和神经退行性疾病相关的认知功能障碍的潜力。
Phosphodiesterases (PDEs) are the only known enzymes to degrade intracellular cyclic AMP and/or cyclic GMP. The PDE superfamily consists of 11 families (PDE1- PDE11), each of which has 1 to 4 subtypes. Some of the subtypes may have multiple splice variants (e.g. PDE4D1-PDE4D11), leading to a total of more than 100 known proteins to date. Growing attention has been paid to the potential of PDEs as therapeutic targets for mood disorders and/or diseases affecting cognitive activity by controlling the rate of hydrolysis of the two aforementioned second messengers in recent years. The loss of cognitive functions is one of the major complaints most patients with CNS diseases face; it has an even more prominent negative impact on the quality of daily life. Cognitive dysfunction is usually a prognosis in patients suffering from neuropsychiatric and neurodegenerative diseases, including depression, schizophrenia, and Alzheimer's disease. This review will focus on the contributions of PDEs to the interface between cognitive deficits and neuropsychiatric and neurodegenerative disorders. It is expected to make for the understanding and discovery that selective PDE inhibitors have the therapeutic potential for cognitive dysfunctions associated with neuropsychiatric and neurodegenerative disorders.