The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation
The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation
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DOI：
10.1016/j.mcn.2018.02.011
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Biswas, Subhas Chandra
中科院分区：
文献类型：
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作者：
Akhter, Rumana;Saleem, Suraiya;Biswas, Subhas Chandra
促凋亡Bcl-2同源3结构域（BH3-only）蛋白是多种生理和病理条件下细胞死亡的主要调节因子，包括阿尔茨海默病（AD）。Bcl-2修饰因子（Bmf）是一种仅涉及bh3的蛋白，与各种死亡模式有关，如心脏病、癫痫、癌症和自身免疫。在各种死亡模式中，它还与其他仅bh3蛋白（如Bim）合作。然而，其在神经退行性变中的作用尚未得到充分研究。在这里，我们首次报道了在β -淀粉样蛋白（A β）毒性或NGF剥夺引起的神经元死亡中，Bmf及其与直接激活剂BH3-only蛋白Bim和Puma的协同作用的重要作用。寡聚物A β是AD的主要病理物种，NGF剥夺与发育性和病理性神经元死亡有关。我们发现，Bmf过表达导致细胞死亡，而Bmf敲低可保护神经元免受A β或NGF剥夺引起的死亡。我们还发现，在A β或NGF剥夺引起的神经元死亡中，Bmf与其他重要的BH3-only蛋白（如Bim和Puma）合作。综上所述，我们的研究结果阐明了Bmf及其与已知的神经元死亡诱导剂Bim和Puma在A β治疗或NGF剥夺引起的神经元死亡中的重要作用。
The pro-apoptotic Bcl-2 homology 3 domain only (BH3-only) proteins are central regulators of cell death in various physiological and pathological conditions, including Alzheimer's disease (AD). Bcl-2 modifying factor (Bmf) is one such BH3-only protein that is implicated in various death paradigms such as anoikis, seizures, cancer and autoimmunity. It also co-operates with other BH3-only proteins such as Bim in various death paradigms. However, its role in neurodegeneration is under-investigated. Here, we report for the first time the essential role of Bmf and its co-operativity with direct activator BH3-only proteins Bim and Puma in neuron death induced by beta-amyloid (A beta) toxicity or NGF deprivation. Oligomeric A beta is main pathologic species in AD and NGF deprivation is relevant for both developmental as well as pathologic neuron death. We find that Bmf over-expression causes cell death and Bmf knockdown protects neurons against death evoked by A beta or NGF deprivation. We also find that Bmf co-operates with other important BH3-only proteins such as Bim and Puma in neuron death induced by A beta or NGF deprivation. Simultaneous knocking down of these molecules by their respective shRNAs provide enhanced protection against A beta Taken together, our results elucidate the essential role of Bmf and its co-operative effects with already known neuron death inducers, Bim and Puma, in neuron death evoked by A beta treatment or NGF deprivation.