Prion疾病和“proteinonly”假说

Prion Diseases and The “Protein only” Hypothesis

Prion病是指一类由蛋白质错误折叠导致的具有传染性的疾病 .人类的纹状体脊髓变性病、库鲁病、脑软化病 ,和致死的家族性失眠症以及动物的羊瘙痒病和牛海绵状脑炎即疯牛病 ,都是致死性的神经退行性疾病 ,它们都属于传染性海绵状脑炎 ,统称Prion病 .PrPC 是Prion蛋白在细胞内的正常形式 ,PrPSc是其致病形式 .根据“proteinonly”假说 ,PrPC 向PrPSc的转化是致病的关键步骤 .简要介绍了PrP蛋白的结构特征、PrPC 向PrPSc转化的可能机制、影响PrPC 向PrPSc转化的重要因素和PrP在细胞内的生物学过程等方面的研究进展 ,讨论了Prion疾病的诊断和治疗方法 .

Prion diseases are thought to arise through misfolding of the cellular protein PrP, which can exist in both cellular, PrP C, and pathological, PrP Sc , forms. According to the “protein only” hypothesis, disease results from infection with the misfolded prion form of the protein, or by inherited mutations in the PrP gene which apparently increase the propensity of the protein to misfold. The result is one of a number of devastating neurological diseases, which are inevitably fatal and are characteristed by spongiform changes in the brain. Hence prion diseases are also known as transmissable spongiform encephalopathies (TSEs). New advances in prion research were reviewed focusing on the structural characteristics of the PrP protein. Putative mechanisms for the conversion between PrP C and PrP Sc , and the factors thought to influence this change, are described. Progress in determining the physiological function of the PrP protein and prospects for diagnosis and treatment are discussed.