中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (12): 2677-2678.doi: 10.4103/1673-5374.338995

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

解决与年龄相关的中枢神经系统髓鞘转换下降和用于少突胶质细胞再生的药物发现

  

  • 出版日期:2022-12-15 发布日期:2022-05-05

Resolving the age-related decline in central nervous system myelin turnover and drug discovery for oligodendroglial rejuvenation

Andrea Domenico Rivera*, Arthur Morgan Butt, Kasum Azim*   

  1. Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, UK (Rivera AD, Butt AM) 
    Section of Human Anatomy, Department of Neuroscience, University of Padua, Padua, Italy (Rivera AD)
    Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany (Azim K) 
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Andrea Domenico Rivera, PhD, andrea.rivera@unipd.it; Kasum Azim, PhD, kasumazim@gmail.com.
  • Supported by:
    This work was supported by a PhD Studentship from The Anatomical Society (to ADR, AMB), and grants from the BBSRC (to AMB, ADR, Grant Number BB/M029379/1), MRC (to AMB, Grant Number MR/P025811/1), Multiple Sclerosis Society of the UK (to AMB; Award Reference: 40), MSCA Seal of Excellence @ UNIPD and NVIDIA Hardware Grant (to ADR), German Research Council (AZ/115/1-1; AZ/115/1-3), Swiss National Funds (to KA; P300PA_171224).

摘要: https://orcid.org/0000-0002-5507-2103 (Andrea Domenico Rivera) 
https://orcid.org/0000-0003-3984-4473 (Kasum Azim)

Abstract: Just over half of the weight of an entire adult human brain is attributed to myelin, which wraps around neuronal axons and is essential for superfast axonal conduction and neuronal integrity. In the central nervous system, it is the function of specialized cells called oligodendrocytes (OLs) to make myelin, which is made up of lipids and proteins. OLs are generated throughout life by a significant population of oligodendrocyte progenitor cells (OPCs) that are responsible for the lifelong generation of OLs and myelin, essential for learning, as well as repair following pathological insults (i.e. in demyelinating diseases that include multiple sclerosis) (Simons and Nave, 2015; Philips and Rothstein, 2017). Changes in myelin content in the human brain over the lifespan of individuals have been well documented, as well as evidence of myelin loss in rodent models using classical histological approaches (Bartzokis et al., 2012; Soreq et al., 2017). During the normal course of aging, degenerative alterations in myelin (myelin thinning, formation of myelin balloons, loss of myelinated tracts) have been shown to precede overt neuronal loss and ultimately lead to negative clinical outcomes, which manifest as the dramatic decline in the speed and efficiency of neuronal networks [reviewed in Rivera et al. (2021a)]. However, a gap in our knowledge was the precise changes in OL and myelin genes at the transcriptome level, which can inform the genetic programs for targeting rejuvenation (Neumann et al., 2019; Rivera et al., 2021b).