Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education of China, Co-innovation Center of Neuroregeneration , Nantong University , Nantong , Jiangsu 226001 , PR China.
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor , New York State Institute for Basic Research in Developmental Disabilities , Staten Island , New York 10314 , United States.
ACS Chem Neurosci. 2019 Feb 20;10(2):931-944. doi: 10.1021/acschemneuro.8b00457. Epub 2018 Oct 23.
Alzheimer's disease (AD), the most common form of dementia, is characterized by extracellular β-amyloid plaques and intracellular neurofibrillary tangles (NFTs), which are considered as major targets for AD therapies. However, no effective therapy is available to cure or prevent the progression of AD up until now. Accumulation of NFTs, which consist of abnormally hyperphosphorylated tau, is directly correlated with the degree of dementia in AD patients. Emerging evidence indicates that the prion-like seeding and spreading of tau pathology may be the key driver of AD. In the past decades, greater understanding of tau pathway reveals new targets for the development of specific therapies. Here, we review the recent research progress in the mechanism underlying tau pathology in AD and briefly introduce tau-based therapeutics.
阿尔茨海默病(AD)是最常见的痴呆症形式,其特征是细胞外β-淀粉样斑块和细胞内神经原纤维缠结(NFTs),这被认为是 AD 治疗的主要靶点。然而,到目前为止,还没有有效的治疗方法可以治愈或阻止 AD 的进展。NFTs 的积累,由异常过度磷酸化的 tau 组成,与 AD 患者的痴呆程度直接相关。新出现的证据表明,tau 病理的类朊病毒样播种和传播可能是 AD 的关键驱动因素。在过去的几十年中,对 tau 通路的深入了解揭示了开发特异性治疗方法的新靶点。在这里,我们综述了 AD 中 tau 病理学的机制的最新研究进展,并简要介绍了基于 tau 的治疗方法。