Laboratory for Molecular Neuroendocrinology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Curr Alzheimer Res. 2010 Dec;7(8):685-96. doi: 10.2174/156720510793611628.
The current review discusses microtubules and tau in the healthy brain and move on to the underling pathology of Alzheimer's disease (AD) with emphasis on tau and neurofibrillary tangles. Tangles have been associated with cognitive dysfunction causing neurodegeneration in the absence of plaques. AD, the most abundant tauopathy is characterized by β-amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of β-amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases. Our own focused research is on activity-dependent neuroprtective protein (ADNP). Our findings show that ADNP-deficiency leads to tauopathy which is inhibited by the ADNP derived drug candidate, davunetide (originally known as NAP). The current review further describes tau as a potential diagnostic marker followed by drug candidates that are aimed at fighting tau pathology. A recent historical perspective is the final comment of the manuscript. This paper is not a comprehensive review of the literature rather it gives my own point of view in the face of many publications and a great unmet need for future therapeutics. It is hoped that davunetide, a most advanced drug in clinical development will rapidly advance as a first effective treatment for a number of brain disorders broadly categorized as frontotemporal dementia (FTD) and serve as a prototype for future therapeutic development toward modification and remedy of currently intractable neurodegenerative diseases.
当前的综述讨论了健康大脑中的微管和 tau，并进一步探讨了阿尔茨海默病（AD）的潜在病理学，重点是 tau 和神经纤维缠结。缠结与认知功能障碍有关，导致斑块缺失的神经退行性变。AD 是最常见的 tau 病，其特征是β-淀粉样斑块和 tau 缠结。大量的 tau 包含物，而没有β-淀粉样沉积物，定义了 Pick 病（额颞叶变性）、进行性核上性麻痹（PSP）、皮质基底节变性（CBD）和其他疾病。我们自己的重点研究是活性依赖性神经保护蛋白（ADNP）。我们的研究结果表明，ADNP 缺乏会导致 tau 病，而 ADNP 衍生的候选药物 davunetide（最初称为 NAP）可以抑制这种疾病。本综述进一步将 tau 描述为一种潜在的诊断标志物，然后介绍了针对 tau 病理学的候选药物。本文的最后一部分是最近的历史观点。本文不是对文献的全面综述，而是在面对众多出版物和未来治疗学的巨大未满足需求时，给出了我自己的观点。希望 davunetide 作为一种处于临床开发后期的最先进药物，能够迅速成为治疗多种广泛归类为额颞叶痴呆（FTD）的脑部疾病的有效药物，并成为针对目前难以治疗的神经退行性疾病的治疗方法的改进和补救的未来治疗方法的原型。
