Ghetti B, Piccardo P, Frangione B, Bugiani O, Giaccone G, Young K, Prelli F, Farlow M R, Dlouhy S R, Tagliavini F
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
Brain Pathol. 1996 Apr;6(2):127-45. doi: 10.1111/j.1750-3639.1996.tb00796.x.
The prion protein (PrP) plays an essential role in the pathogenesis of a group of sporadic, genetically determined and infectious fatal degenerative diseases, referred to as "prion diseases", affecting the central nervous system of humans and other mammals. The cellular PrP is encoded by a single copy gene, highly conserved across mammalian species. In prion diseases, PrP undergoes conformational changes involving a shift from alpha-helix to beta-sheet structure. This conversion is important for PrP amyloidogenesis, which occurs to the highest degree in the genetically determined Gerstmann-Sträussler-Scheinker disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA), while it is less frequently seen in other prion diseases. GSS and PrP-CAA are associated with point mutations of the prion protein gene (PRNP); these conditions show a broad spectrum of clinical presentation, the main signs being ataxia, spastic paraparesis, extrapyramidal signs and dementia. In GSS, parenchymal amyloid may be associated with spongiform changes or neurofibrillary lesions; in PrP-CAA, vascular amyloid is associated with neurofibrillary lesions. A major component of the amyloid fibrils in the two diseases is a 7 kDa peptide, spanning residues 81-150 of PrP.
朊病毒蛋白（PrP）在一组散发性、遗传性和传染性致命退行性疾病（称为“朊病毒病”）的发病机制中起着至关重要的作用，这些疾病会影响人类和其他哺乳动物的中枢神经系统。细胞型PrP由单拷贝基因编码，在哺乳动物物种中高度保守。在朊病毒病中，PrP会发生构象变化，包括从α螺旋结构转变为β折叠结构。这种转变对于PrP淀粉样变性很重要，在遗传性格斯特曼-施特劳斯勒-谢inker病（GSS）和朊病毒蛋白脑淀粉样血管病（PrP-CAA）中淀粉样变性程度最高，而在其他朊病毒病中则较少见。GSS和PrP-CAA与朊病毒蛋白基因（PRNP）的点突变有关；这些病症表现出广泛的临床症状，主要体征为共济失调、痉挛性截瘫、锥体外系体征和痴呆。在GSS中，实质淀粉样变可能与海绵状改变或神经原纤维病变有关；在PrP-CAA中，血管淀粉样变与神经原纤维病变有关。这两种疾病中淀粉样纤维的主要成分是一种7 kDa的肽，跨越PrP的81-150位残基。
