Dominguez-Meijide Antonio, Vasili Eftychia, Outeiro Tiago Fleming
Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, 37073 Goettingen, Germany.
Laboratory of Neuroanatomy and Experimental Neurology, Dept. of Morphological Sciences, CIMUS, IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Brain Sci. 2020 Nov 13;10(11):858. doi: 10.3390/brainsci10110858.
Tauopathies are neurodegenerative disorders characterized by the deposition of aggregates composed of abnormal tau protein in the brain. Additionally, misfolded forms of tau can propagate from cell to cell and throughout the brain. This process is thought to lead to the templated misfolding of the native forms of tau, and thereby, to the formation of newer toxic aggregates, thereby propagating the disease. Therefore, modulation of the processes that lead to tau aggregation and spreading is of utmost importance in the fight against tauopathies. In recent years, several molecules have been developed for the modulation of tau aggregation and spreading. In this review, we discuss the processes of tau aggregation and spreading and highlight selected chemicals developed for the modulation of these processes, their usefulness, and putative mechanisms of action. Ultimately, a stronger understanding of the molecular mechanisms involved, and the properties of the substances developed to modulate them, will lead to the development of safer and better strategies for the treatment of tauopathies.
tau蛋白病是一类神经退行性疾病,其特征是大脑中由异常tau蛋白组成的聚集体沉积。此外,错误折叠的tau蛋白形式可在细胞间以及整个大脑中传播。这个过程被认为会导致天然形式的tau蛋白发生模板化错误折叠,从而形成新的有毒聚集体,进而使疾病传播。因此,调节导致tau蛋白聚集和扩散的过程在对抗tau蛋白病中至关重要。近年来,已经开发了几种用于调节tau蛋白聚集和扩散的分子。在这篇综述中,我们讨论了tau蛋白聚集和扩散的过程,并重点介绍了为调节这些过程而开发的选定化学物质、它们的用途以及假定的作用机制。最终,对所涉及的分子机制以及为调节这些机制而开发的物质的特性有更深入的了解,将有助于开发更安全、更好的治疗tau蛋白病的策略。