教授
神經退行性疾病🏭，如阿爾茲海默病𓀝、帕金森病和漸凍人症等，是威脅人類健康的重大神經疾病。神經退行性疾病的發生與衰老密切相關𓀋，發生機理涉及復雜的分子、細胞和組織水平的進行性的病變。人類對於復雜神經系統的認識一直是科學研究的重大挑戰，對於神經系統疾病發生的理解尤為艱難。然而👖，欲行其事，先通其理🥎🌿。縱然舉步維艱，EON体育4平台對於神經系統認識的每一次進步🕐，都將讓EON体育4平台離神經退行性疾病的治療更近。本課題組致力於揭示神經退行性疾病的發生發展機製🤗、臨床早期檢測方法的建立和藥物的開發。
蛋白質穩態是維持細胞功能所必需的🤳。在衰老的過程中，蛋白質穩態的失衡與神經退行性疾病發生密切相關♝。各種神經退行性疾病都對應不同蛋白的異常聚集。在行使正常生物學功能的過程中🐧，很多蛋白會通過分相和聚集，組裝成大的分子機器和無膜細胞器。蛋白正常的高分子聚集和病理性異常聚集往往只有一線之隔。衰老過程中細胞內蛋白質量監控的減弱，使得蛋白異常聚集得以積累，進一步損害細胞功能，甚至導致細胞死亡。這一過程在神經退行性疾病的發展過程中不斷上演。
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(東方學者)
2020年 中組部萬人計劃青年拔尖
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