铝是广泛接触的神经毒物，过量接触引起认知功能损害，铝神经毒性机制主要为突触可塑性损害和神经细胞凋亡。铝离子易进入细胞核，对染色体有凝聚作用，促进连接组蛋白与核心组蛋白的结合，从而使神经细胞正常转录抑制。最新研究提示组蛋白赖氨酸甲基化修饰通过H3K4甲基转移酶MLL - H3K4me3水平 - Egr1和BDNF表达三级调控链调节学习记忆功能。我们推测铝通过干扰MLL的PHD锌指结构域，抑制了上述环节，损害突触可塑性，降低学习记忆功能。本课题通过铝接触职业人群队列研究，动物体内实验、高表达MLL细胞株体外实验，研究铝致H3K4甲基转移酶MLL抑制- H3K4me3水平改变-Egr1和BDNF表达改变在铝致学习记忆损害和神经细胞凋亡中的作用，阐明在铝作用下该调控链中各环节的作用机制，从表观遗传角度研究铝的神经毒性，为探讨铝致认知功能损害机制提供新资料，并尝试将上述蛋白作为铝致神经毒性生物标志。

Aluminum is a widely exposed neurotoxicant. Excessive exposure to aluminum induces cognitive impairment. Synaptic plasticity impairment and neural apoptosis are main toxic mechanism caused by aluminum.Aluminum ions enters easily into nucleus and aggregate chromosomes, and promote binding of linker histones with core histones,thus inhibit normal gene transcription in neural cells. Recent research indicated that histone lysine methylation modification regulates learning and memory function via H3K4 methyltransferase MLL-H3K4mes level-Egr1 and BDNF expression, a three leveled regulation chain. We suppose that aluminum might interfer with PHD zinc finger domain of MLL, inhibit chain of MLL-H3K4mes-Egr1 and BDNF described above, impair synaptic plasticity and decrease learning and memory ability. With occupationally Al-exposed population cohort prospective study,in vivo study, and in vitro study with MLL highly expressed cell lines , we explore effects of H3K4 methyltransferase inhibition- MLL-H3K4mes level variation-Egr1 and BDNF expression on aluminum-induced learning & memory impairment and neural apoptosis, and clarify the effect mechanism of every link of this regulation chain, in order to investigate aluminum-induced neurotoxicity from the viewpoint of epigenetics. Furthermore, This study not only provides new informations for investigating the mechanism of aluminum-induced cognitive impaiment, but also try to take these proteins as biomarkers for Al-induced neurotoxicity.