Lathe Richard, Darlix Jean-Luc
Division of Infection and Pathway Medicine, University of Edinburgh, Edinburgh, UK.
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
J Alzheimers Dis Rep. 2017 Dec 16;1(1):263-275. doi: 10.3233/ADR-170037.
The prion protein PRNP has been centrally implicated in the transmissible spongiform encephalopathies (TSEs), but its normal physiological role remains obscure. We highlight emerging evidence that PRNP displays antimicrobial activity, inhibiting the replication of multiple viruses, and also interacts directly with Alzheimer's disease (AD) amyloid-β (Aβ) peptide whose own antimicrobial role is now increasingly secure. PRNP and Aβ share share membrane-penetrating, nucleic acid binding, and antiviral properties with classical antimicrobial peptides such as LL-37. We discuss findings that binding of abnormal nucleic acids to PRNP leads to oligomerization of the protein, and suggest that this may be an entrapment and sequestration process that contributes to its antimicrobial activity. Some antimicrobial peptides are known to be exploited by infectious agents, and we cover evidence that PRNP is usurped by herpes simplex virus (HSV-1) that has evolved a virus-encoded 'anti-PRNP'.unction. These findings suggest that PRNP, like LL-37 and Aβ, is likely to be a component of the innate immune system, with implications for the pathoetiology of both AD and TSE.
朊病毒蛋白PRNP一直被认为在传染性海绵状脑病（TSEs）中起核心作用，但其正常生理功能仍不清楚。我们着重介绍新出现的证据，即PRNP具有抗菌活性，可抑制多种病毒的复制，并且还直接与阿尔茨海默病（AD）的淀粉样β蛋白（Aβ）相互作用，而Aβ自身的抗菌作用现在也越来越明确。PRNP和Aβ与经典抗菌肽如LL-37一样，具有膜穿透、核酸结合和抗病毒特性。我们讨论了异常核酸与PRNP结合导致该蛋白寡聚化的研究结果，并认为这可能是一个捕获和隔离过程，有助于其抗菌活性。已知一些抗菌肽会被病原体利用，我们还阐述了单纯疱疹病毒1型（HSV-1）篡夺PRNP功能并进化出病毒编码的“抗PRNP”功能的证据。这些发现表明，PRNP与LL-37和Aβ一样，可能是先天免疫系统的一个组成部分，这对AD和TSE的发病机制都有影响。
