Krüger Lars, Mandelkow Eva Maria
German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany; Caesar Research Center, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany; Max-Planck-Institute for Metabolism Research, Hamburg Outstation, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany.
Curr Opin Neurobiol. 2016 Feb;36:52-8. doi: 10.1016/j.conb.2015.09.004. Epub 2015 Sep 29.
Pathological Tau is a hallmark of various neuronal disorders and spreads in the brain of Alzheimer patients in a well-defined manner. Beside Tau's main function in stabilizing microtubules for axonal transport, a variety of novel functions for neurons and glia have emerged recently. Tau regulates the susceptibility to hyperexcitation and plays a role in neuron-glia contact formation. Studies implicate soluble oligomeric species of Tau, rather than insoluble aggregates, as more detrimental to proper neuronal function. Tau is not exclusively intracellular; instead Tau can be released into the extracellular space. This has led to the hypothesis of a prion-disease like mechanism to explain the stereotypical progression of Tau. Targeting pathological Tau with antibodies or aggregation inhibitors may help to prevent pathology.
病理性tau蛋白是多种神经疾病的标志,并以一种明确的方式在阿尔茨海默病患者的大脑中扩散。除了tau蛋白在稳定微管以进行轴突运输方面的主要功能外,最近还发现了其对神经元和神经胶质细胞的多种新功能。tau蛋白调节神经元对过度兴奋的易感性,并在神经元与神经胶质细胞接触形成中发挥作用。研究表明,tau蛋白的可溶性寡聚体而非不溶性聚集体对正常神经元功能更具损害性。tau蛋白并非仅存在于细胞内;相反,它可以释放到细胞外空间。这导致了一种类似朊病毒疾病机制的假说,以解释tau蛋白的典型进展。用抗体或聚集抑制剂靶向病理性tau蛋白可能有助于预防病变。