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 (Aβ) toxicity or NGF deprivation. Oligomeric Aβ 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 Aβ 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 Aβ or NGF deprivation. Simultaneous knocking down of these molecules by their respective shRNAs provide enhanced protection against Aβ. 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 Aβ treatment or NGF deprivation.

促凋亡的仅Bcl-2同源3结构域（仅BH3）蛋白是各种生理和病理状况（包括阿尔茨海默氏病（AD））中细胞死亡的主要调节剂。Bcl-2修饰因子（Bmf）是这样一种仅BH3的蛋白质，与多种死亡范例有关，例如无神经症，癫痫发作，癌症和自身免疫。它还在各种死亡范例中与仅BH3的其他蛋白质（例如Bim）合作。然而，其在神经变性中的作用尚未得到充分研究。在这里，我们首次报道了Bmf的基本作用及其与直接激活蛋白BH3唯一的蛋白Bim和Puma在β-淀粉样蛋白（Aβ）毒性或NGF剥夺诱导的神经元死亡中的协同作用。寡聚Aβ是AD中的主要病理学种类，而NGF剥夺与发育以及病理性神经元死亡均相关。我们发现Bmf的过度表达会导致细胞死亡，而Bmf的敲低可以保护神经元免受Aβ或NGF剥夺引起的死亡。我们还发现Bmf与其他重要的仅BH3的重要蛋白（例如Bim和Puma）在Aβ或NGF剥夺诱导的神经元死亡中协同作用。通过它们各自的shRNA同时敲低这些分子可增强针对Aβ的保护。两者合计，我们的结果阐明了Bmf的基本作用及其与已知神经元死亡诱导物Bim和Puma在Aβ治疗或NGF剥夺引起的神经元死亡中的协同作用。我们还发现Bmf与其他重要的仅BH3的重要蛋白（例如Bim和Puma）在Aβ或NGF剥夺诱导的神经元死亡中协同作用。通过它们各自的shRNA同时敲低这些分子可增强针对Aβ的保护。两者合计，我们的结果阐明了Bmf的基本作用及其与已知神经元死亡诱导物Bim和Puma在Aβ治疗或NGF剥夺引起的神经元死亡中的协同作用。我们还发现Bmf与其他重要的仅BH3的重要蛋白（例如Bim和Puma）在Aβ或NGF剥夺诱导的神经元死亡中协同作用。通过它们各自的shRNA同时敲低这些分子可增强针对Aβ的保护。两者合计，我们的结果阐明了Bmf的基本作用及其与已知神经元死亡诱导物Bim和Puma在Aβ治疗或NGF剥夺引起的神经元死亡中的协同作用。