朊蛋白在神经系统作用机制研究进展

Research advances in the mechanism of action of prion protein in the nervous system

摘要:

细胞型朊蛋白(PrP^C)作为一种跨膜糖蛋白在哺乳动物中广泛存在。基因敲除的研究显示PrP^C在神经系统的活动中的关键作用包括周围神经髓鞘的形成以及对神经毒素刺激的保护。PrP^C在不同的细胞类型中也有不同的生物学作用。如PrP^C模块化结构、多种结合伴侣以及与脂质筏的密切关联的特性，使其具有组装多组分复合物的能力，从而触发不同的信号通路，调节细胞分化。PrP^C在大脑中参与的病理性作用仍然没有一致的定论，其错误折叠产生的异构体PrP^SC是朊病毒疾病的主要致病因素。但有证据指出PrP^C在朊病毒疾病中发挥的致病作用独立于羊瘙痒病朊蛋白亚型(PrP^SC)，在朊病毒感染过程中，朊病毒疾病的临床和神经病理症状与大脑中PrP^C而不是PrP^SC的表达水平成正比。另外，PrP^C可能还是一种与神经退行性病变相关的蛋白，参与β淀粉样蛋白(Aβ)等聚集性蛋白的神经毒素信号转导，还充当α-突触核蛋白的细胞受体，促进其在细胞吸收以及大脑中传播。虽然朊病毒的研究已经取得很大的进展,但PrP^C在大脑中的作用仍然没有明确，因此探索PrP^C在细胞中作用具有十分重要的意义。国际神经病学神经外科学杂志, 2021, 48(1): 86-89］

Abstract:

Cellular prion protein （PrP^C） widely exists in mammals as a transmembrane glycoprotein， and gene-knockout studies have shown that PrP^C plays a key role in the activity of the nervous system， including peripheral nerve myelination and protection against neurotoxic stimuli. PrP^C has different biological functions in different cell types. With the features of a modular structure， multiple binding partners， and close association with lipid rafts， PrP^C has the function to assemble multicomponent complexes， trigger different signaling pathways， and regulate cell differentiation. No consensus has been reached on the pathological role of PrP^C in the brain， and the scrapie isoform of the prion protein （PrP^SC） formed by misfolding is a main pathogenic factor for prion diseases. However， evidence has shown that the pathogenic effect of PrP^C in prion diseases is independent of PrP^SC， and during prion infection， clinical and neuropathological symptoms of prion diseases are positively correlated with the expression of PrP^C rather than PrP^SC. In addition， PrP^C may also be a protein associated with neurodegenerative diseases and participates in the neurotoxic signal transduction for protein aggregates including β-amyloid， and it also acts as a cellular receptor of α-synuclein to promote its cell uptake and spread in the brain. Although great achievements have been made in the research on prion， the role of PrP^C in brain remains unclear， and therefore， it is of great significance to explore the role of PrP^C in cells.Journal of International Neurology and Neurosurgery, 2021, 48(1): 86-89］