Therapeutic principles on protein misfolding diseases

治疗囊性纤维化和家族性淀粉样多发性神经病的药物开发仍在进行中。我们发现了囊性纤维化的主要突变体ΔF508 CFTR和甲状腺素运载蛋白变体的细胞内蛋白质质量控制机制，从而提出了家族性淀粉样多发性神经病药物开发的新概念。此外，我们发现，内质网相关的甲状腺素运载蛋白变体的降解是负调控的BiP在哺乳动物细胞中。

Drug development for cystic fibrosis and familial amyloid polyneuropathy is still in progress. We found out the intracellular protein quality control mechanisms of ΔF508 CFTR, a major mutant of cystic fibrosis, and of transthyretin variants, resulting in proposal of new concept of drug development for familial amyloid polyneuropathy. In addition, we found that the endoplasmic reticulum-associated degradation of transthyretin variants is negatively regulated by BiP in mammalian cells.