Qiu Chenxi, Li Zhixiong, Leigh David A, Duan Bingbing, Stucky Joseph E, Kim Nami, Xie George, Lu Kun Ping, Zhou Xiao Zhen
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Departments of Biochemistry and Oncology, Schulich School of Medicine and Dentistry and Robarts Research Institute, Western University, London, ON, Canada.
Front Cell Dev Biol. 2024 Apr 2;12:1343962. doi: 10.3389/fcell.2024.1343962. eCollection 2024.
Tauopathies are neurodegenerative diseases characterized by deposits of abnormal Tau protein in the brain. Conventional tauopathies are often defined by a limited number of Tau epitopes, notably neurofibrillary tangles, but emerging evidence suggests structural heterogeneity among tauopathies. The prolyl isomerase Pin1 isomerizes P-tau to inhibit the development of oligomers, tangles and neurodegeneration in multiple neurodegenerative diseases such as Alzheimer's disease, traumatic brain injury, vascular contribution to cognitive impairment and dementia (VCID) and preeclampsia (PE). Thus, P-tau has emerged as an early etiological driver, blood marker and therapeutic target for multiple neurodegenerative diseases, with clinical trials ongoing. The discovery of P-tau and other tau pathologies in VCID and PE calls attention for simplistic classification of tauopathy in neurodegenerative diseases. These recent advances have revealed the exciting novel role of the Pin1- P-tau axis in the development and treatment of vascular contribution to cognitive impairment and dementia and preeclampsia.
tau蛋白病是一类神经退行性疾病，其特征是大脑中异常tau蛋白沉积。传统的tau蛋白病通常由有限数量的tau表位定义，特别是神经原纤维缠结，但新出现的证据表明tau蛋白病之间存在结构异质性。脯氨酰异构酶Pin1将磷酸化tau（P-tau）异构化，以抑制多种神经退行性疾病（如阿尔茨海默病、创伤性脑损伤、血管性认知障碍和痴呆（VCID）以及子痫前期（PE））中寡聚体、缠结和神经退行性变的发展。因此，P-tau已成为多种神经退行性疾病的早期病因驱动因素、血液标志物和治疗靶点，目前临床试验正在进行。在VCID和PE中发现P-tau和其他tau病变，提醒人们注意神经退行性疾病中tau蛋白病的简单分类。这些最新进展揭示了Pin1-P-tau轴在血管性认知障碍和痴呆以及子痫前期的发生发展和治疗中的令人兴奋的新作用。
