Martins V R, Graner E, Garcia-Abreu J, de Souza S J, Mercadante A F, Veiga S S, Zanata S M, Neto V M, Brentani R R
Fundação Antônio Prudente, São Paulo, Brazil.
Nat Med. 1997 Dec;3(12):1376-82. doi: 10.1038/nm1297-1376.
Prions, the etiological agents for infectious degenerative encephalopathies, act by entering the cell and inducing conformational changes in PrPC (a normal cell membrane sialoglycoprotein), which result in cell death. A specific cell-surface receptor to mediate PrPC and prion endocytosis has been predicted. Complementary hydropathy let us generate a hypothetical peptide mimicking the receptor binding site. Antibodies raised against this peptide stain the surface of mouse neurons and recognize a 66-kDa membrane protein that binds PrPC both in vitro and in vivo. Furthermore, both the complementary prion peptide and antiserum against it inhibit the toxicity of a prion-derived peptide toward neuronal cells in culture. Such reagents might therefore have therapeutic applications.
朊病毒是传染性退行性脑病的病原体，其作用方式是进入细胞并诱导朊蛋白（一种正常的细胞膜唾液酸糖蛋白）发生构象变化，从而导致细胞死亡。据预测，存在一种介导朊蛋白和朊病毒内吞作用的特异性细胞表面受体。互补亲水性分析使我们能够生成一种模拟受体结合位点的假设性肽段。针对该肽段产生的抗体可对小鼠神经元表面进行染色，并识别一种66 kDa的膜蛋白，该蛋白在体外和体内均可结合朊蛋白。此外，互补朊病毒肽及其抗血清均可抑制朊病毒衍生肽对培养的神经元细胞的毒性。因此，这类试剂可能具有治疗应用价值。
