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该研究揭示了神经退行性疾病蛋白的可溶性单体构象存在“多态性”,导致构象依赖的不同的降解速率,进而产生不同的毒性。该发现不仅刷新了科学家对疾病机制的认识,并且提供了治疗疾病的新思路:例如可寻找化合物迫使疾病蛋白从慢速降解的构象转变为快速降解的构象,从而治疗疾病。该发现也揭示了选择性自噬比之前科学家所认识的还要更具选择性:它不仅能识别特定的蛋白降解,甚至能识别同一蛋白的不同构象。
由于对选择性自噬的抵抗性,具有过长的多聚谷氨酰胺序列的变异亨廷顿蛋白降解速度更慢,毒性更强。
复旦大学博士后付玉华、硕士生吴鹏、潘宇寅和青年副研究员孙晓俐为此论文并列第一作者,鲁伯埙为此论文的唯一通讯作者。复旦大学为论文的第一单位及通讯单位。该研究获得了国家重点研发罕见病项目、国家自然科学基金委重大研究计划及优秀青年项目等的资助。鲁伯埙研究员自2013年初在复旦大学生命科学学院创建实验室以来,以通讯作者的身份在相关领域国际知名期刊发表论文多篇。
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