Departments of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA.
Curr Alzheimer Res. 2011 Sep;8(6):666-77. doi: 10.2174/156720511796717195.
Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of Alzheimer's disease (AD) and are primarily composed of aggregates of hyperphosphorylated forms of the microtubule associated protein tau. It is likely that an imbalance of kinase and phosphatase activities leads to the abnormal phosphorylation of tau and subsequent aggregation. The wide ranging therapeutic approaches that are being developed include to inhibit tau kinases, to enhance phosphatase activity, to promote microtubule stability, and to reduce tau aggregate formation and/or enhance their clearance with small molecule drugs or by immunotherapeutic means. Most of these promising approaches are still in preclinical development whilst some have progressed to Phase II clinical trials. By pursuing these lines of study, a viable therapy for AD and related tauopathies may be obtained.
神经原纤维缠结(NFTs)是阿尔茨海默病(AD)的病理特征之一,主要由微管相关蛋白 tau 的过度磷酸化形式聚集而成。很可能是由于激酶和磷酸酶活性的失衡导致 tau 的异常磷酸化和随后的聚集。正在开发的广泛的治疗方法包括抑制 tau 激酶、增强磷酸酶活性、促进微管稳定性,以及用小分子药物或免疫治疗手段减少 tau 聚集形成和/或增强其清除。这些有希望的方法中的大多数仍处于临床前开发阶段,而有些方法已进展到 II 期临床试验。通过进行这些研究,可以获得针对 AD 和相关 tau 病的可行疗法。