Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-Ku, Tokyo, 162-8480, Japan.
Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-Cho, Shinjuku-Ku, Tokyo, 162-8480, Japan.
Neuromolecular Med. 2024 Nov 12;26(1):45. doi: 10.1007/s12017-024-08814-0.
Neurodegenerative disease characterized by the progressive damage of the nervous system, and neuropathies caused by the neuronal injury are both led to substantial impairments in neural function and quality of life among geriatric populations. Recovery from nerve damage and neurodegenerative diseases present a significant challenge, as the central nervous system (CNS) has limited capacity for self-repair. Investigating mechanism of neurodegeneration and regeneration is essential for advancing our understanding and development of effective therapies for nerve damage and degenerative conditions, which can significantly enhance patient outcomes. Collapsin response mediator protein 2 (CRMP2) was first identified as a key mediator of axonal growth and guidance is essential for neurogenesis and neuroregeneration. Phosphorylation as a primary modification approach of CRMP2 facilitates its involvement in numerous physiological processes, including axonal guidance, neuroplasticity, and cytoskeleton dynamics. Prior research on CRMP2 phosphorylation has elucidated its involvement in the mechanisms of neurodegenerative diseases and nerve damage. Pharmacological and genetic interventions that alter CRMP2 phosphorylation have shown the potential to influence neurodegenerative diseases and promote nerve regeneration. Even with decades of research delving into the intricacies of CRMP2 phosphorylation, there remains a scarcity of comprehensive literature reviews addressing this topic. This absence of synthesis and integration of findings hampers the field's progress by preventing a holistic understanding of CRMP2's implications in neurobiology, thereby impeding potential advancements in clinical treatments and interventions. This review intends to compile investigations focused on the role of CRMP2 phosphorylation in both neurodegenerative disease models and injury models to summarizing impacts and offer novel insight for clinical therapies.
神经退行性疾病的特征是神经系统的进行性损伤,神经元损伤引起的神经病变导致老年人群的神经功能和生活质量严重受损。神经损伤和神经退行性疾病的恢复带来了重大挑战,因为中枢神经系统(CNS)自我修复的能力有限。研究神经退行性变和再生的机制对于我们理解和开发有效的神经损伤和退行性疾病治疗方法至关重要,这可以显著改善患者的预后。 collapsin 反应介质蛋白 2(CRMP2)最初被鉴定为轴突生长和导向的关键介质,对于神经发生和神经再生至关重要。磷酸化作为 CRMP2 的主要修饰方法之一,促进了其参与众多生理过程,包括轴突导向、神经可塑性和细胞骨架动力学。先前关于 CRMP2 磷酸化的研究阐明了其在神经退行性疾病和神经损伤机制中的作用。改变 CRMP2 磷酸化的药理学和遗传学干预表明,它们有可能影响神经退行性疾病并促进神经再生。尽管对 CRMP2 磷酸化进行了几十年的研究,但仍缺乏全面的文献综述来解决这一主题。这种缺乏对研究结果的综合和整合,通过阻止对 CRMP2 在神经生物学中的意义的全面理解,阻碍了该领域的进展,从而阻碍了临床治疗和干预的潜在进展。本综述旨在汇编聚焦于 CRMP2 磷酸化在神经退行性疾病模型和损伤模型中的作用的研究,总结其影响,并为临床治疗提供新的见解。