Huber A B, Schwab M E
Brain Research Institute, Department of Neuromorphology, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland.
Biol Chem. 2000 May-Jun;381(5-6):407-19. doi: 10.1515/BC.2000.053.
The lack of regrowth of injured neurons in the adult central nervous system (CNS) of higher vertebrates was accepted as a fact for many decades. In the last few years a very different view emerged; regeneration of lesioned fibre tracts in vivo could be induced experimentally, and molecules that are responsible for inhibition and repulsion of growing neurites have been defined. Mechanisms that link cellular phenomena like growth cone turning or growth cone collapse to intracellular changes in second messenger systems and cytoskeletal dynamics became unveiled. This article reviews recent developments in this field, focusing especially on one of the best characterised neurite out-growth inhibitory molecules found in CNS myelin that was recently cloned: Nogo-A. Nogo-A is a high molecular weight transmembrane protein and an antigen of the monoclonal antibody mAb IN-1 that was shown to promote long-distance regeneration and functional recovery in vivo when applied to spinal cord-injured adult rats. Nogo-A is expressed by oligodendrocytes in white matter of the CNS. With the molecular characterisation of this factor new possibilities open up to achieve structural and functional repair of the injured CNS.
几十年来,高等脊椎动物成体中枢神经系统(CNS)中受损神经元无法再生被视作一个事实。在过去几年里,出现了一种截然不同的观点;体内受损纤维束的再生可以通过实验诱导,并且已经明确了负责抑制和排斥生长中神经突的分子。将诸如生长锥转向或生长锥塌陷等细胞现象与第二信使系统和细胞骨架动力学的细胞内变化联系起来的机制也已被揭示。本文综述了该领域的最新进展,尤其聚焦于中枢神经系统髓鞘中发现的一种特征最为明确的神经突生长抑制分子,该分子最近已被克隆:Nogo - A。Nogo - A是一种高分子量跨膜蛋白,也是单克隆抗体mAb IN - 1的抗原,当将其应用于脊髓损伤的成年大鼠时,该抗体在体内可促进长距离再生和功能恢复。Nogo - A由中枢神经系统白质中的少突胶质细胞表达。随着该因子的分子特性被阐明,为实现受损中枢神经系统的结构和功能修复开辟了新的可能性。