磷酸二酯酶4抑制剂罗氟司特改善认知功能研究进展

Advances in studies of cognition enhancement by phosphodiesterase-4 inhibitor roflumilast

罗氟司特(roflumilast)是2011年美国FDA批准用于治疗慢性阻塞性肺疾病的第二代磷酸二酯酶4(PDE4)抑制剂,具有抗炎、抗肿瘤、抗酒精成瘾和抗糖尿病等多种作用。近年发现,与其他PDE4抑制剂一样,其也具有神经保护作用,尤其对认知功能具有一定改善作用。在多种动物模型上,可改善诱导的认知功能障碍,并能有效改善患者的认知功能。因此,罗氟司特可能作为潜在的阿尔茨海默病和帕金森病等中枢神经退行性疾病治疗药物。其作用机制主要与调控cAMP信号转导通路及相关信号分子有关。本文对其非临床和临床研究的最新进展进行了综述。

Roflumilast,one of the second generation of phosphodiesterase-4 inhibitors,has been approved for the treatment of severe chronic obstructive pulmonary disease by the United States Food and Drug Administration since 2011.It has shown a variety of beneficial effects,including anti-inflammatory,anti-tumor,anti-alcoholic,and anti-diabetic profiles.Recent studies have demonstrated that roflumilast,like other PDE4 inhibitors,has neuroprotective and precognitive properties.It also has been shown to produce promising cognitive improvement in animals and humans.Therefore,roflumilast can be a potential drug for treatment of various degenerative diseases of the central nervous system,including Alzheimer disease and Parkinson disease.The major mechanism is the activation of cyclic AMP signaling and its downstream targeting molecules.All these are discussed and summarized in the current review.