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髓磷脂蛋白老化并分解这一事实能否解释某些人多发性硬化症的发病原因?

Can the Fact That Myelin Proteins Are Old and Break down Explain the Origin of Multiple Sclerosis in Some People?

作者信息

Truscott Roger J W, Friedrich Michael G

机构信息

Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.

出版信息

J Clin Med. 2018 Sep 14;7(9):281. doi: 10.3390/jcm7090281.

Abstract

Recent discoveries may change the way that multiple sclerosis (MS) is viewed, particularly with regard to the reasons for the untoward immune response. The fact that myelin proteins are long-lived, and that by the time we are adults, they are extensively degraded, alters our perspective on the reasons for the onset of autoimmunity and the origin of MS. For example, myelin basic protein (MBP) from every human brain past the age of 20 years, is so greatly modified, that it is effectively a different protein from the one that was laid down in childhood. Since only a subset of people with such degraded MBP develop MS, a focus on understanding the mechanism of immune responses to central nervous system (CNS) antigens and cerebral immune tolerance appear to be worthwhile avenues to explore. In accord with this, it will be productive to examine why all people, whose brains contain large quantities of a "foreign antigen", do not develop MS. Importantly for the potential causation of MS, MBP from MS patients breaks down differently from the MBP in aged controls. If the novel structures formed in these MS-specific regions are particularly antigenic, it could help explain the origin of MS. If verified, these findings could provide an avenue for the rational synthesis of drugs to prevent and treat MS.

摘要

最近的发现可能会改变人们看待多发性硬化症(MS)的方式,尤其是在引发不良免疫反应的原因方面。髓磷脂蛋白寿命很长,到我们成年时,它们已被大量降解,这一事实改变了我们对自身免疫性疾病发病原因以及MS起源的看法。例如,20岁以上每个人大脑中的髓磷脂碱性蛋白(MBP)都有很大程度的修饰,实际上它与童年时期形成的蛋白质已截然不同。由于只有一部分MBP发生这种降解的人会患上MS,因此专注于理解针对中枢神经系统(CNS)抗原的免疫反应机制以及大脑免疫耐受似乎是值得探索的途径。与此一致的是,研究为什么所有大脑中含有大量“外来抗原”的人都不会患上MS将会有所收获。对于MS的潜在病因而言重要的是,MS患者的MBP与老年对照组的MBP分解方式不同。如果在这些MS特异性区域形成的新结构具有特别的抗原性,这可能有助于解释MS的起源。如果得到证实,这些发现可能为合理合成预防和治疗MS的药物提供一条途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/898a/6162792/f444dc8647d3/jcm-07-00281-g001.jpg

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