Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Department of Neurology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Expert Rev Neurother. 2021 Sep;21(9):983-991. doi: 10.1080/14737175.2021.1965882. Epub 2021 Sep 2.
The cellular prion protein (PrP), some of its derivatives (especially PrP N-terminal N1 peptide and shed PrP), and PrP-containing exosomes have strong neuroprotective activities, which have been reviewed in the companion article (Part I) and are briefly summarized here. We propose that elevating the extracellular levels of a protective PrP form using gene therapy and other approaches is a very promising novel avenue for prophylactic and therapeutic treatments against prion disease, Alzheimer's disease, and several other neurodegenerative diseases. We will dissect the pros and cons of various potential PrP-based treatment options and propose a few strategies that are more likely to succeed. The cited references were obtained from extensive PubMed searches of recent literature, including peer-reviewed original articles and review articles. Concurrent knockdown of celllular PrP expression and elevation of the extracellular levels of a neuroprotective PrP N-terminal peptide via optimized gene therapy vectors is a highly promising broad-spectrum prophylactic and therapeutic strategy against several neurodegenerative diseases, including prion diseases, Alzheimer's disease and Parkinson's disease.
细胞朊病毒蛋白（PrP）、其一些衍生物（尤其是 PrP N 端 N1 肽和脱落的 PrP）和含有 PrP 的外泌体具有很强的神经保护活性，这在相关文章（第一部分）中已经进行了综述，在此简要概述。我们提出，使用基因治疗和其他方法提高细胞外保护性 PrP 形式的水平是预防和治疗朊病毒病、阿尔茨海默病和其他几种神经退行性疾病的一种很有前途的新方法。我们将剖析各种潜在 PrP 治疗选择的优缺点，并提出一些更有可能成功的策略。所引用的参考文献是通过对最近文献（包括同行评议的原始文章和综述文章）的广泛 PubMed 搜索获得的。通过优化的基因治疗载体同时敲低细胞朊病毒蛋白的表达并提高神经保护性 PrP N 端肽的细胞外水平，是针对包括朊病毒病、阿尔茨海默病和帕金森病在内的几种神经退行性疾病的一种极具前景的广谱预防和治疗策略。
