Department of Experimental Medicine University of Milano-Bicocca, via Cadore 48, 20052 Monza, Italy.
Curr Alzheimer Res. 2011 Sep;8(6):615-22. doi: 10.2174/156720511796717140.
Neurodegenerative diseases termed Tauopathies, including Alzheimer disease, are characterized by the presence of intraneuronal neurofibrillary tangles (NFTs), composed by hyperphosphorylated protein Tau. Peptidyl-prolyl cis/trans isomerase Pin1 plays a pivotal role in the regulation of Tau phosphorylation/dephosphorylation state. Indeed, Pin1 specifically recognizes pThr231-Pro232 motif of Tau, catalyzes its isomerisation and, in dependence of the cellular environment, promotes its dephosphorylation by PP2A phosphatase: in the dephosphorylated state Tau is able to exert its physiological activity, promoting microtubules polymerization. However, Pin1 activity in Tauopathies in which Tau is mutated can be harmful, because the isomerase can accelerate progression of the disease. Taking into account the complexity of pathways in which Pin1, under a strict regulation, exerts its biological functions, this isomerase can be consider a promising target in the improvement and design of new therapies against Tauopathies.
神经退行性疾病称为 Tau 病，包括阿尔茨海默病，其特征是存在神经元内神经原纤维缠结（NFTs），由过度磷酸化的 Tau 蛋白组成。肽基脯氨酰顺/反异构酶 Pin1 在调节 Tau 磷酸化/去磷酸化状态方面起着关键作用。事实上，Pin1 特异性识别 Tau 的 pThr231-Pro232 基序，催化其异构化，并根据细胞环境促进其被 PP2A 磷酸酶去磷酸化：在去磷酸化状态下，Tau 能够发挥其生理活性，促进微管聚合。然而，在 Tau 病中，当 Tau 发生突变时，Pin1 的活性可能是有害的，因为异构酶可以加速疾病的进展。考虑到 Pin1 在严格调控下发挥其生物学功能的途径的复杂性，这种异构酶可以被认为是改善和设计针对 Tau 病的新疗法的有希望的靶点。
