Abstract:
Aggregation of the microtubule-associated protein tau (MAPT) is the hallmark pathology in a spectrum of neurodegenerative disorders collectively called tauopathies. Physiologically, tau is an inherent neuronal protein that plays an important role in the assembly of microtubules and axonal transport. However, disease-associated mutations of this protein reduce its binding to the microtubule components and promote self-aggregation, leading to formation of tangles in neurons. Tau is also expressed in oligodendrocytes, where it has significant developmental roles in oligodendrocyte maturation and myelin synthesis. Oligodendrocyte-specific tau pathology, in the form of fibrils and coiled coils, is evident in major tauopathies including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick\'s disease (PiD). Multiple animal models of tauopathy expressing mutant forms of MAPT recapitulate oligodendroglial tau inclusions with potential to cause degeneration/malfunction of oligodendrocytes and affecting the neuronal myelin sheath. Till now, mechanistic studies heavily concentrated on elucidating neuronal tau pathology. Therefore, more investigations are warranted to comprehensively address tau-induced pathologies in oligodendrocytes. The present review provides the current knowledge available in the literature about the intricate relations between tau and oligodendrocytes in health and diseases.
摘要:
微管相关蛋白tau(MAPT)的聚集是一系列神经退行性疾病中的标志性病理,统称为tau蛋白病。生理学上,tau是一种固有的神经元蛋白,在微管的组装和轴突运输中起着重要作用。然而,这种蛋白质的疾病相关突变减少了其与微管成分的结合并促进了自身聚集,导致神经元中缠结的形成。Tau也在少突胶质细胞中表达,在少突胶质细胞成熟和髓磷脂合成中具有重要的发育作用。少突胶质细胞特异性tau病理学,以原纤维和卷曲螺旋的形式,在包括进行性核上性麻痹(PSP)在内的主要tau蛋白病变中明显,皮质基底变性(CBD),和皮克病(PiD)。表达突变形式的MAPT的tau蛋白病的多种动物模型概括了少突胶质tau包涵体,有可能导致少突胶质细胞变性/功能障碍并影响神经元髓鞘。到现在为止,机械研究主要集中在阐明神经元tau病理学。因此,有必要进行更多的研究,以全面解决少突胶质细胞中tau诱导的病变。本综述提供了文献中有关tau和少突胶质细胞在健康和疾病中的复杂关系的最新知识。