Lloret A, Fuchsberger T, Giraldo E, Viña J
Department of Physiology, Faculty of Medicine, University of Valencia and Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, 46010 Valencia, Spain.
Department of Physiology, Faculty of Medicine, University of Valencia and Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, 46010 Valencia, Spain.
Free Radic Biol Med. 2015 Jun;83:186-91. doi: 10.1016/j.freeradbiomed.2015.02.028. Epub 2015 Mar 5.
Neurofibrillary tangles (aggregates of cytoskeletal Tau protein) and senile plaques (aggregates mainly formed by amyloid β peptide) are two landmark lesions in Alzheimer׳s disease. Some researchers have proposed tangles, whereas others have proposed plaques, as primary lesions. For a long time, these were thought of as independent mechanisms. However, experimental evidence suggests that both lesions are intimately related. We review here some molecular pathways linking amyloid β and Tau toxicities involving, among others, glycogen synthase kinase 3β, p38, Pin1, cyclin-dependent kinase 5, and regulator of calcineurin 1. Understanding amyloid β and Tau toxicities as part of a common pathophysiological mechanism may help to find molecular targets to prevent or even treat the disease.
神经原纤维缠结（细胞骨架Tau蛋白聚集体）和老年斑（主要由淀粉样β肽形成的聚集体）是阿尔茨海默病的两个标志性病变。一些研究人员提出缠结是原发性病变，而另一些人则提出斑块是原发性病变。长期以来，这些被认为是独立的机制。然而，实验证据表明这两种病变密切相关。我们在此综述一些连接淀粉样β和Tau毒性的分子途径，其中包括糖原合酶激酶3β、p38、Pin1、细胞周期蛋白依赖性激酶5和钙调神经磷酸酶1调节因子。将淀粉样β和Tau毒性理解为共同病理生理机制的一部分，可能有助于找到预防甚至治疗该疾病的分子靶点。
