Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed To Be University), Kalinga Nagar, Bhubaneswar, 751003, India.
Neurobiology Laboratory, Centre for Biotechnology, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed To Be University), Kalinga Nagar, Bhubaneswar, 751003, India.
Cell Mol Neurobiol. 2021 Aug;41(6):1157-1174. doi: 10.1007/s10571-020-00893-4. Epub 2020 Jun 5.
In the last few decades, cytoplasmic organellar dysfunction, such as that of the endoplasmic reticulum (ER), has created a new area of research interest towards the development of serious health maladies including neurodegenerative diseases. In this context, the extensively dispersed family of ER-localized proteins, i.e. reticulons (RTNs), is gaining interest because of its regulative control over neural regeneration. As most neurodegenerative diseases are pathologically manifested with the accretion of misfolded proteins with subsequent induction of ER stress, the regulatory role of RTNs in neural dysfunction cannot be ignored. With the limited information available in the literature, delineation of the functional connection between rising consequences of neurodegenerative diseases and RTNs need to be elucidated. In this review, we provide a broad overview on the recently revealed regulatory roles of reticulons in the pathophysiology of several health maladies, with special emphasis on neurodegeneration. Additionally, we have also recapitulated the decisive role of RTN4 in neurite regeneration and highlighted how neurodegeneration and proteinopathies are mechanistically linked with each other through specific RTN paralogues. With the recent findings advocating zebrafish Rtn4b (a mammalian Nogo-A homologue) downregulation following central nervous system (CNS) lesion, RTNs provides new insight into the CNS regeneration. However, there are controversies with respect to the role of Rtn4b in zebrafish CNS regeneration. Given these controversies, the connection between the unique regenerative capabilities of zebrafish CNS by distinct compensatory mechanisms and Rtn4b signalling pathway could shed light on the development of new therapeutic strategies against serious neurodegenerative diseases.
在过去的几十年中，细胞质细胞器功能障碍，如内质网 (ER)，已经为严重健康疾病的发展创造了一个新的研究领域，包括神经退行性疾病。在这种情况下，广泛分布的内质网定位蛋白家族，即 reticulons (RTNs)，由于其对神经再生的调节控制作用而引起了人们的兴趣。由于大多数神经退行性疾病的病理表现为错误折叠蛋白的积累，随后引发内质网应激，因此 RTNs 在神经功能障碍中的调节作用不容忽视。由于文献中提供的信息有限，需要阐明神经退行性疾病的后果与 RTNs 之间的功能联系。在这篇综述中，我们提供了一个广泛的概述，介绍了最近发现的 reticulons 在几种健康疾病的病理生理学中的调节作用，特别强调了神经退行性变。此外，我们还总结了 RTN4 在轴突再生中的决定性作用，并强调了神经退行性变和蛋白病如何通过特定的 RTN 同源物在机制上相互联系。最近的研究结果表明，斑马鱼 Rtn4b（一种哺乳动物 Nogo-A 同源物）在中枢神经系统 (CNS) 损伤后下调，这为 CNS 再生提供了新的见解。然而，关于 Rtn4b 在斑马鱼 CNS 再生中的作用存在争议。鉴于这些争议，通过独特的补偿机制和 Rtn4b 信号通路的斑马鱼 CNS 的独特再生能力之间的联系，可以为针对严重神经退行性疾病的新治疗策略的发展提供启示。
