教授
蛋白质稳态是维持细胞功能所必需的。在衰老的过程中，蛋白质稳态的失衡与神经退行性疾病发生密切相关。各种神经退行性疾病都对应不同蛋白的异常聚集。在行使正常生物学功能的过程中，很多蛋白会通过分相和聚集，组装成大的分子机器和无膜细胞器。蛋白正常的高分子聚集和病理性异常聚集往往只有一线之隔。衰老过程中细胞内蛋白质量监控的减弱，使得蛋白异常聚集得以积累，进一步损害细胞功能，甚至导致细胞死亡。这一过程在神经退行性疾病的发展过程中不断上演。
神经退行性疾病，如阿尔兹海默病、帕金森病和渐冻人症等，是威胁人类健康的重大神经疾病。神经退行性疾病的发生与衰老密切相关，发生机理涉及复杂的分子、细胞和组织水平的进行性的病变。人类对于复杂神经系统的认识一直是科学研究的重大挑战，对于神经系统疾病发生的理解尤为艰难。然而，欲行其事，先通其理。纵然举步维艰，我们对于神经系统认识的每一次进步，都将让我们离神经退行性疾病的治疗更近。本课题组致力于揭示神经退行性疾病的发生发展机制、临床早期检测方法的建立和药物的开发。
Tao Y.Q., Sun Y.P., Lv S.R., Xia W.C., Zhao K., Xu Q.H., Zhao Q.Y., He L., Wang Y., Liu C.*, Li D.* Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology. Nat Commun. 2022 Jul 22;13(1):4226.
Long H.F., Zhang S.N., Zeng S.Y., Tong Y.L., Liu J., Liu C.*, Li D.* Interaction of RAGE with α-synuclein fibrils mediates inflammatory response of microglia. Cell Rep, 2022 Sep 20;40(12):111401
Li D*, Liu C*. Conformational strains of pathogenic amyloid proteins in neurodegenerative diseases. Nat Rev Neurosci. 2022 Sep;23(9):523-534.
Fan Y, Zhao Q, Xia W, Tao Y, Yu W, Chen M, Liu Y, Zhao J, Shen Y, Sun Y, Si C, Zhang S, Zhang Y, Li W, Liu C, Wang J*, Li D*. Generic amyloid fibrillation of TMEM106B in patient with Parkinson's disease dementia and normal elders. Cell Res. 2022 Jun;32(6):585-588.
Yunpeng Sun#, Kun Zhao#, Wencheng Xia, Jinge Gu, Yeyang Ma, Xinrui Gui, Xia Zhang, Yanshan Fang, Bo Sun, Cong Liu*, Dan Li* The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure, Nature Communications, 2020, Dec 11.
Jinge Gu , Zhenying Liu , Shengnan Zhang , Yichen Li , Wencheng Xia , Chen Wang , Huaijiang Xiang , Zhijun Liu , Li Tan , Yanshan Fang , Cong Liu* , Dan Li*, Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles, PNAS, 2020, Dec 8.
Zhao, K., Li, Y., Liu, Z., Long, H., Zhao, C., Luo, F., Sun, Y., Tao, Y., Su, X.-D., Li, D.#, Li, X.#, Liu, C.#, Parkinson’s disease associated mutation E46K of α-synuclein triggers the formation of a distinct fibril structure. Nature Communications, 2020 , May 26.
Gui, X., Luo, F., Li, YC, Zhou, H., Qin,Z., Liu, ZY, Gu, JG, Xie, MY, Zhao, K., Dai, B., Shin, WS, He, JH, He, L., Jiang, L., Zhao, ML, Sun, B., Li, XM, Liu, C.#, Li, D.# Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly, Nature Communications, 2019 May 1;10(1):2006.
2019年 上海高校特聘教授(东方学者)
2020年 中组部万人计划青年拔尖
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