Crosstalk between the mTOR and Nrf2/ARE signaling pathways as a target in the improvement of long-term potentiation.

TitleCrosstalk between the mTOR and Nrf2/ARE signaling pathways as a target in the improvement of long-term potentiation.
Publication TypeJournal Article
Year of Publication2020
AuthorsGureev AP, Popov VN, Starkov AA
JournalExp Neurol
Volume328
Pagination113285
Date Published2020 Jun
ISSN1090-2430
Abstract

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.

DOI10.1016/j.expneurol.2020.113285
Alternate JournalExp. Neurol.
PubMed ID32165256
PubMed Central IDPMC7145749
Grant ListP01 AG014930 / AG / NIA NIH HHS / United States