CCT2分泌与内吞的机制及其对毒性蛋白聚集体传递的影响

随着人口老龄化问题日趋严重，神经退行性疾病患者日益增加。毒性蛋白聚集体的形成是导致神经退行性疾病的重要原因之一。毒性蛋白聚集体的传递加重了神经退行性疾病的进程。我们之前的研究表明，CCT2能够作为聚集体自噬受体，特异性地清除细胞内的固态毒性蛋白聚集体。我们近期的研究发现，CCT2还能够被分泌到细胞外，而胞外的CCT2可以被内吞进入细胞，这一过程影响了毒性蛋白的分泌与内吞。因此，我们猜测CCT2在调控毒性蛋白传递中发挥重要作用。为此，本研究将探索CCT2分泌与内吞的具体机制，以找到调控CCT2分泌与内吞的方式。通过在神经元与小胶质细胞中选择性调控CCT2及其介导的毒性蛋白的分泌与内吞，我们希望能够促进毒性蛋白聚集体从神经元到小胶质细胞的传递，从而达到保护神经元并促进小胶质细胞吞噬与降解蛋白聚集体的目的。我们的研究将为治疗神经退行性疾病提供新的思路。

With aging of the population, the number of patients with neurodegenerative diseases is increasing. The formation of toxic protein aggregates is one of the important causes of neurodegenerative diseases. The spread of toxic protein aggregates aggravates the process of neurodegenerative diseases. Our previous studies have indicated that CCT2 can act as an aggrephagy receptor to specifically clear intracellular solid protein aggregates. Recently, we found that CCT2 can be secreted into the extracellular space, and the extracellular CCT2 can be endocytosed into cells, which affects the secretion and endocytosis of toxic protein. Therefore, we hypothesized that CCT2 plays an important role in regulating toxic protein spread. Therefore, this study will explore the specific mechanism of CCT2 secretion and endocytosis to find the way to regulate CCT2 secretion and endocytosis. By selectively regulating the secretion and endocytosis of CCT2 and toxic proteins in neurons and microglia, we hope to promote the transmission of toxic protein aggregates from neurons to microglia, thereby protecting neurons and promoting the phagocytosis and degradation of protein aggregates by microglia. Our study will provide new insight for the treatment of neurodegenerative diseases.