Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia.
Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia; Voronezh State University of Engineering Technologies, Voronezh, Russia.
Exp Neurol. 2020 Jun;328:113285. doi: 10.1016/j.expneurol.2020.113285. Epub 2020 Mar 10.
In recent years, a significant progress was made in understanding molecular mechanisms of long-term memory. Long-term memory formation requires strengthening of neuronal connections (LTP, long-term potentiation) associated with structural rearrangement of neurons. The key role in the synthesis of proteins essential for these rearrangements belong to mTOR (mammalian target of rapamycin) complexes and signaling pathways involved in mTOR regulation. Suppression of mTOR activity may impair synaptic plasticity and long-term memory, while mTOR activation inhibits autophagy, thereby potentiating amyloidosis and development of Alzheimer's disease (AD) accompanied by irreversible memory loss. Because of this, suppression/inhibition of mTOR might have unpredictable consequences on memory. The Nrf2/ARE signaling pathway affects almost all mitochondrial processes. The activation of this pathway improves memory and exhibits therapeutic effect in AD. In this review, we discuss the crosstalk between the Nrf2/ARE signaling and mTOR in the maintenance of synaptic plasticity. Nrf2 pathway can be activated by pharmacological agents and by changes in mitochondria functioning accompanying various neuronal dysfunctions.
近年来，人们在理解长期记忆的分子机制方面取得了重大进展。长期记忆的形成需要增强神经元之间的连接（LTP，长时程增强），这与神经元的结构重排有关。在合成这些重排所必需的蛋白质中，mTOR（哺乳动物雷帕霉素靶蛋白）复合物及其参与 mTOR 调节的信号通路起着关键作用。mTOR 活性的抑制可能会损害突触可塑性和长期记忆，而 mTOR 的激活会抑制自噬，从而增强淀粉样蛋白沉积和阿尔茨海默病（AD）的发展，并伴有不可逆转的记忆丧失。因此，mTOR 的抑制/失活可能对记忆产生不可预测的后果。Nrf2/ARE 信号通路几乎影响所有的线粒体过程。该通路的激活可以改善记忆，并在 AD 中显示出治疗效果。在这篇综述中，我们讨论了 Nrf2/ARE 信号与 mTOR 在维持突触可塑性方面的相互作用。Nrf2 通路可以通过药理学制剂和伴随各种神经元功能障碍的线粒体功能变化来激活。
