6月3日 彭勃:小胶质细胞更替与替换——从基础研究到临床治疗(知名学者系列学术报告)

时间:2025-06-03浏览:13设置

讲座题目:小胶质细胞更替与替换——从基础研究到临床治疗

主讲人:彭勃 教授

主持人:李大力 研究员

开始时间:2025-6-3 15:00

讲座地址:闵行校区生科楼159会议室

主办单位:生命科学学院


报告人简介:

彭勃,复旦大学特聘教授,博士生导师,国家优青,科技部重大项目首席科学家,爱思唯尔中国高被引学者,教育部科技领军人才团队负责人,上海市领军人才。获得钟南山青年科技创新奖、华夏医学科技青年奖等荣誉。担任脑科学转化研究院院长助理,教育部免疫炎症疾病原创药物医药基础研究创新中心副主任,中国细胞生物学会神经细胞分会副会长,中国神经科学学会胶质细胞分会副主任委员,中国微循环学会神经免疫专委会副主任委员,上海市神经科学学会理事。 彭勃教授主要关注中枢神经系统内的小胶质细胞,系统性阐明其衰老、死亡和再生的更替机制。以此为基础,创新性提出以小胶质细胞替换开展神经系统疾病治疗的新策略,并在国际上首次实现高效的小胶质细胞替换(2020)。进一步,团队全球首次开展小胶质细胞替换临床治疗,证明该疗法的有效性(2024),为神经系统疾病治疗开辟了全新思路。主要研究成果以最后通讯作者发表在Science,Nature Neuroscience,Nature Aging,Neuron,Cell Reports,Nature Comms和eLife等高水平期刊上,入选神经免疫学年度科学进展。


报告内容:

Microglia undergo turnover throughout the lifespan. Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia in adult mice. The origin of repopulated microglia has been hotly debated. We investigated the origin of repopulated microglia and demonstrated that all repopulated microglia were derived from the proliferation of the few surviving microglia (<1%). To dissect functions of aged microglia excluding the influence from other aged brain cells, we utilized 3-round depletion-repopulation (3xDR) to accelerate microglial turnover without directly affecting other brain cells. By this model, we achieved aged-like microglia in non-aged brains and confirmed that aged-like microglia per se contribute to cognitive decline. Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by allogenic cells has been proposed to treat microglia-associated disorders. However, some attempts have failed due to low replacement efficiency. Based on our understanding in microglial repopulation, we develop three efficient strategies for microglia replacement with diverse application scenarios and demonstrate the therapeutic effects in CSF1R-associated microgliopathy (CAMP, aka ALSP, HDLS or CRLE). It thus opens up a window on treating microglia-associated CNS disorders. Besides, clearance of microglial debris is crucial for CNS homeostasis. If microglial debris is not timely removed, it may influence CNS function. We find that although microglia can phagocytose microglial debris in vitro, the territory-dependent competition hinders the microglia-to-microglial debris engulfment in vivo. In contrast, microglial debris is mainly phagocytosed by astrocytes in the brain, facilitated by C4b opsonization and degraded by noncanonical autophagy. Together, we elucidated mechanisms of microglia turnover and developed novel therapeutic approaches for neurological disorders.


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