Faculty of Medicine, McGill University, Montreal, QC H3A 0G4, Canada.
Flogen Technologies Inc., Mount Royal, QC H3P 2T1, Canada.
Int J Mol Sci. 2024 Nov 15;25(22):12268. doi: 10.3390/ijms252212268.
Memory impairment is caused by the absence of the 4E-BP2 protein in the brain. This protein undergoes deamidation spontaneously in the neurons. 4E-BP2 deamidation significantly alters protein synthesis in the neurons and affects the balance of protein production required for a healthy nervous system. Any imbalance in protein production in the nervous system causes neurodegenerative diseases. Discovering what causes 4E-BP2 deamidation will make it possible to control this balance of protein production and develop effective treatments against neurodegenerative diseases such as Alzheimer's and Parkinson's. The purpose of this work is to discover the neurobiological mechanism that causes the deamidation reaction in the 4E-BP2 protein by performing immunoblotting in the retinal ganglia, the optic nerve, the dorsal root ganglia, the sciatic nerve, and the whole brain, extracted via dissection from 2-month-old, Wild-type male mice. The results show that axons and their unique properties cause neuron-specific 4E-BP2 deamidation in the nervous system, confirming conclusively that axons are the critical factors behind the fundamental neurobiological mechanism of 4E-BP2 protein deamidation.
记忆损伤是由大脑中缺乏 4E-BP2 蛋白引起的。这种蛋白质在神经元中会自发地发生脱酰胺作用。4E-BP2 的脱酰胺作用会显著改变神经元中的蛋白质合成，影响健康神经系统所需的蛋白质产生平衡。神经系统中蛋白质产生的任何失衡都会导致神经退行性疾病。发现导致 4E-BP2 脱酰胺的原因将能够控制这种蛋白质产生的平衡，并开发针对阿尔茨海默病和帕金森病等神经退行性疾病的有效治疗方法。本工作的目的是通过对从 2 个月大的野生型雄性小鼠中提取的视网膜神经节、视神经、背根神经节、坐骨神经和整个大脑进行免疫印迹，发现导致 4E-BP2 蛋白脱酰胺反应的神经生物学机制。结果表明，轴突及其独特性质导致神经系统中神经元特异性 4E-BP2 脱酰胺，这确凿地证实了轴突是 4E-BP2 蛋白脱酰胺基本神经生物学机制背后的关键因素。
