Upadhyay Arun, Amanullah Ayeman, Chhangani Deepak, Mishra Ribhav, Mishra Amit
Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan 342011, India.
Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan 342011, India.
Ageing Res Rev. 2015 Nov;24(Pt B):138-59. doi: 10.1016/j.arr.2015.07.009. Epub 2015 Aug 3.
Efficient and regular performance of Ubiquitin Proteasome System and Autophagy continuously eliminate deleterious accumulation of nonnative protiens. In cellular quality control system, E3 ubiquitin ligases are significant employees for defense mechanism against abnormal toxic proteins. Few findings indicate that lack of functions of E3 ubiquitin ligases can be a causative factor of neurodevelopmental disorders, neurodegeneration, cancer and ageing. However, the detailed molecular pathomechanism implying E3 ubiquitin ligases in cellular functions in multifactorial disease conditions are not well understood. This article systematically represents the unique characteristics, molecular nature, and recent developments in the knowledge of neurobiological functions of few crucial E3 ubiquitin ligases. Here, we review recent literature on the roles of E6-AP, HRD1 and ITCH E3 ubiquitin ligases in the neuro-pathobiological mechanisms, with precise focus on the processes of neurodegeneration, and thereby propose new lines of potential targets for therapeutic interventions.
泛素蛋白酶体系统和自噬的高效且规律的运行持续消除非天然蛋白质的有害积累。在细胞质量控制系统中,E3泛素连接酶是抵御异常毒性蛋白防御机制的重要成员。少数研究结果表明,E3泛素连接酶功能缺失可能是神经发育障碍、神经退行性变、癌症和衰老的致病因素。然而,在多因素疾病条件下,E3泛素连接酶在细胞功能中的详细分子病理机制尚不清楚。本文系统地阐述了几种关键E3泛素连接酶的独特特征、分子性质以及神经生物学功能知识的最新进展。在此,我们综述了近期关于E6-AP、HRD1和ITCH E3泛素连接酶在神经病理生物学机制中作用的文献,特别关注神经退行性变过程,从而提出潜在治疗干预靶点的新思路。