Zhang Jian-Nan, Koch Jan C
Department of Neurology, University Medicine Göttingen, Göttingen, Germany.
Department of Neurobiology, Beijing Institute for Brain Disorders and Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing, China.
Neural Regen Res. 2017 May;12(5):692-695. doi: 10.4103/1673-5374.206631.
Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic approaches should optimally both attenuate axonal degeneration and foster axonal regeneration. Compelling evidence suggests that collapsin response mediator protein-2 (CRMP2) might be a molecular target fulfilling these requirements. In this mini-review, we give a compact overview of the known functions of CRMP2 and its molecular interactors in neurite outgrowth and in neurodegenerative conditions. Moreover, we discuss in detail our recent findings on the role of CRMP2 in acute axonal degeneration in the optic nerve. We found that the calcium influx induced by the lesion activates the protease calpain which cleaves CRMP2, leading to impairment of axonal transport. Both calpain inhibition and CRMP2 overexpression effectively protected the proximal axons against acute axonal degeneration. Taken together, CRMP2 is further characterized as a central molecular player in acute axonal degeneration and thus evolves as a promising therapeutic target to both counteract axonal degeneration and foster axonal regeneration in neurodegenerative and neurotraumatic diseases.
轴突退变是许多神经疾病的关键病理特征。由于中枢神经系统中的轴突无法再生，它常常导致持续性功能缺损。因此，治疗方法应既能最佳地减轻轴突退变，又能促进轴突再生。有力证据表明，塌陷反应介导蛋白2（CRMP2）可能是满足这些要求的一个分子靶点。在本综述中，我们简要概述了CRMP2及其分子相互作用蛋白在神经突生长和神经退行性疾病中的已知功能。此外，我们详细讨论了我们最近关于CRMP2在视神经急性轴突退变中作用的发现。我们发现，损伤诱导的钙内流激活了蛋白酶钙蛋白酶，后者切割CRMP2，导致轴突运输受损。抑制钙蛋白酶和过表达CRMP2均能有效保护近端轴突免受急性轴突退变。综上所述，CRMP2被进一步确定为急性轴突退变的核心分子参与者，因此有望成为治疗神经退行性疾病和神经创伤性疾病中对抗轴突退变和促进轴突再生的靶点。
