中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 701-704.doi: 10.4103/1673-5374.314291

• 综述:神经损伤修复保护与再生 •    下一篇

全面了解p75神经营养蛋白受体的功能及其在大脑中的相互作用

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Towards a comprehensive understanding of p75 neurotrophin receptor functions and interactions in the brain

Joel F. Ritala1, Seán B. Lyne2, Antti Sajanti1, Romuald Girard2, Janne Koskimäki1, 3, 4, *   

  1. 1Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital and University of Turku, Turku, Finland; 2Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, USA; 3Department of Psychiatry, Central Hospital of Southern Ostrobothnia, Seinäjoki, Finland; 4Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Janne Koskimäki, MD, PhD, jj.koskimaki@gmail.com.

摘要: Neural Regen Res:数据挖掘与生物信息学分析p75NTR的生物学作用
    神经营养素在神经可塑性中的作用是近年来神经再生研究领域的一个热点,试图阐明这些分子调节突触、改变损伤反应和改变适应反应的生物学机制。有趣的是,先前的研究强调了p75神经营养素受体(p75NTR)在各种损伤和疾病中的作用,如中枢神经系统损伤、阿尔茨海默病和肌萎缩侧索硬化症。更全面的机制阐明,针对这些分子信号网络的治疗可能允许损伤后的神经元组织再生。众所周知,p75NTR在神经元发育中起着重要作用,一些连锁基因的发现进一步阐明了这一作用。MAGEL2与NRAGE属于同一黑色素瘤相关抗原(MAGE)家族。与NRAGE如何参与p75NTR介导的程序性细胞死亡相似,MAGEL2与诸如Prader-Willi综合征和Schaaf-Yang综合征等神经发育障碍有关,因此表明MAGEL2在人类神经元发育中具有重要意义。先前的动物研究也表明,mTOR和自噬途径在Magel2空白小鼠模型中失调,进一步强调这些失调的过程可能是导致神经元发育改变的潜在病理变化。
    来自芬兰图尔库大学医院的Janne Koskimäki团队认为MAGEL2与转录因子E2F1直接相连,后者与p75NTR直接相连,表明了necdin相关MAGE蛋白在p75NTR功能中的作用,这得到了先前临床前观察的支持,可能是未来研究的一个富有成果的领域。系统化的数据挖掘方法不仅限于p75NTR的研究,还可以应用于其他疾病、机制和网络的研究。有趣的是,7个亚网络连锁基因中的两个,UBC和EP300,在脑可塑性方面还没有被广泛研究。这两个连锁基因及其编码的蛋白质可能是未来研究的重要靶点,以探讨它们与急性脑损伤或神经退行性疾病的关系。研究结果不仅为进一步的研究发现了新的可能的靶基因,而且也验证了先前进行的研究,这些研究确定了主要假说的生物学功能的途径、基因和簇。
文章在《中国神经再生研究(英文版)》杂志2022年 4月 4 期发表。


https://orcid.org/0000-0002-2311-6327 (Janne Koskimäki)

Abstract: The role of neurotrophins in neuronal plasticity has recently become a strong focus in neuroregeneration research field to elucidate the biological mechanisms by which these molecules modulate synapses, modify the response to injury, and alter the adaptation response. Intriguingly, the prior studies highlight the role of p75 neurotrophin receptor (p75NTR) in various injuries and diseases such as central nervous system injuries, Alzheimer’s disease and amyotrophic lateral sclerosis. More comprehensive elucidation of the mechanisms, and therapies targeting these molecular signaling networks may allow for neuronal tissue regeneration following an injury. Due to a diverse role of the p75NTR in biology, the body of evidence comprising its biological role is diffusely spread out over numerous fields. This review condenses the main evidence of p75NTR for clinical applications and presents new findings from published literature how data mining approach combined with bioinformatic analyses can be utilized to gain new hypotheses in a molecular and network level.

Key words: bioinformatics, brain injury, data mining, neuron, neurotrophins, p75NTR, plasticity, regeneration