Panza Francesco, Solfrizzi Vincenzo, Seripa Davide, Imbimbo Bruno P, Lozupone Madia, Santamato Andrea, Tortelli Rosanna, Galizia Ilaria, Prete Camilla, Daniele Antonio, Pilotto Alberto, Greco Antonio, Logroscino Giancarlo
Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, & Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Department of Clinical Research in Neurology, University of Bari Aldo Moro, 'Pia Fondazione Cardinale G. Panico,' Tricase, Lecce, Italy.
Immunotherapy. 2016 Sep;8(9):1119-34. doi: 10.2217/imt-2016-0019.
Pharmacological manipulation of tau protein in Alzheimer's disease included microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation inhibitors, active and passive immunotherapies and, more recently, inhibitors of tau acetylation. Animal studies have shown that both active and passive approaches can remove tau pathology and, in some cases, improve cognitive function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the recent discontinuation of the monoclonal antibody RG7345 for Alzheimer's disease, two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in Phase I testing for progressive supranuclear palsy. After the recent impressive results in animal studies obtained by salsalate, the dimer of salicylic acid, inhibitors of tau acetylation are being actively pursued.
阿尔茨海默病中tau蛋白的药物调控包括微管稳定剂、tau蛋白激酶抑制剂、tau聚集抑制剂、主动和被动免疫疗法，以及最近的tau乙酰化抑制剂。动物研究表明，主动和被动方法都可以消除tau病理，在某些情况下还可以改善认知功能。两种分别针对非磷酸化tau（AAD-vac1）和磷酸化tau（ACI-35）的主动疫苗已进入I期试验。尽管最近用于阿尔茨海默病的单克隆抗体RG7345试验终止，但另外两种抗tau抗体BMS-986168和C2N-8E12目前也在进行针对进行性核上性麻痹的I期试验。在水杨酸二聚体水杨酸盐最近在动物研究中取得令人印象深刻的结果之后，tau乙酰化抑制剂正在积极研发中。
