Abstract:
Tau protein was discovered as a microtubule-associated protein nearly 50 years ago, and our understanding of tau has revolved around that role. Even with tau\'s rise to stardom as a central player in neurodegenerative disease, therapeutic efforts have largely been targeted toward cytoskeletal changes. While some studies hinted toward non-cytoskeletal roles for tau, it is only fairly recently that these ideas have begun to receive considerable attention. Many new binding partners for tau have been identified, including DNA, RNA, RNA-binding proteins, some receptors, and other tau molecules. The diversity of tau binding partners coupled with the discovery of tau other than axonal compartments such as nucleus, dendrites, and synapses have led to the proposal of novel functions for tau in roles such as nuclear stability, cell signaling, transcriptional processing, and protein synthesis. Tau self-assembly in particular has made an impact, leading to the hypothesis that a prion-like function of hyperphosphorylated tau is central to tauopathies. With tau emerging as a multifaceted protein that operates in many parts of the cell and with many molecular partners, the field of tau biology is primed for discoveries that can provide new perspectives on both the unique biochemistry of tau and the nature of devastating neurological diseases.
摘要:
Tau蛋白是近50年前发现的一种微管相关蛋白,我们对tau的理解围绕着这个角色。即使tau作为神经退行性疾病的中心角色成为明星,治疗努力主要针对细胞骨架的改变.虽然一些研究暗示了tau的非细胞骨架作用,直到最近,这些想法才开始受到相当大的关注。已经确定了许多新的tau结合伙伴,包括DNA,RNA,RNA结合蛋白,一些受体,和其他tau分子。tau结合配偶体的多样性加上除了轴突区室如细胞核以外的tau的发现,树突,和突触导致了tau在核稳定等角色中的新功能的提出,细胞信号,转录加工,和蛋白质合成。特别是tau自组装产生了影响,导致了这样的假设,即高度磷酸化tau蛋白的朊病毒样功能是tau蛋白病的核心。随着tau成为一种多层面的蛋白质,在细胞的许多部分和许多分子伴侣中运作,tau生物学领域的发现可以为tau的独特生物化学和破坏性神经系统疾病的性质提供新的视角。