Caughey B
Laboratory of Persistent Viral Diseases, National Institute for Allergy and Infectious Diseases, Hamilton, Montana 59840.
Br Med Bull. 1993 Oct;49(4):860-72. doi: 10.1093/oxfordjournals.bmb.a072651.
Transmissible spongiform encephalopathies (TSEs), Alzheimer's disease and other amyloidoses result in the accumulation of abnormally stable, potentially amyloidogenic proteins that appear to play central roles in disease pathogenesis. Scrapie-infected tissue culture cells have become well-developed models for studying how the TSE-specific protein, protease-resistant PrP, is made from its apparently normal precursor. The conversion of PrP to the protease-resistant state occurs on the plasma membrane or along an endocytic pathway to the lysosomes. The protease-resistant PrP has a much longer half-life than normal PrP and its accumulation in lysosomes may feature in TSE pathogenesis. Congo red and certain sulfated glycans potently inhibit protease-resistant PrP formation or stabilization in cell culture. These and other observations suggest that an interaction of PrP with glycosaminoglycans is critical in protease-resistant PrP accumulation and raises the possibility that therapeutic strategies for TSEs and other amyloidoses could be based on blocking (pre)amyloid-glycosaminoglycan interactions.
传染性海绵状脑病（TSEs）、阿尔茨海默病和其他淀粉样变性病会导致异常稳定的、潜在的淀粉样蛋白生成蛋白的积累，这些蛋白似乎在疾病发病机制中起核心作用。感染瘙痒病的组织培养细胞已成为研究TSE特异性蛋白——抗蛋白酶PrP如何从其看似正常的前体产生的成熟模型。PrP转化为抗蛋白酶状态发生在质膜上或沿着内吞途径至溶酶体。抗蛋白酶PrP的半衰期比正常PrP长得多，其在溶酶体中的积累可能是TSE发病机制的特征。刚果红和某些硫酸化聚糖能有效抑制细胞培养中抗蛋白酶PrP的形成或稳定。这些及其他观察结果表明，PrP与糖胺聚糖的相互作用对抗蛋白酶PrP的积累至关重要，并增加了TSEs和其他淀粉样变性病的治疗策略可能基于阻断（前）淀粉样蛋白-糖胺聚糖相互作用的可能性。
