Abstract
The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging.
Highlights
The mammalian target of rapamycin is a serine/threonine kinase that is involved in the control of cell growth and proliferation
Contrary to what has been observed in other cases, this activation causes long-term memory impairment and amnesic-like effects, probably due to the fact that cannabinoid 1 receptor (CB1R) is mainly expressed in GABAergic interneurons. These findings suggest that the activation of mammalian target of rapamycin (mTOR) through CB1R would contribute to an imbalance between the excitatory and inhibitory inputs in the hippocampus (Puighermanal et al, 2009)
Expression of dominant-negative S6K in the medial prefrontal cortex (mPFC) resulted in prodepressive behavior in the forced swim test and was sufficient to cause anhedonia in the absence of chronic stress exposure. These data demonstrate a critical role for S6 kinase (S6K1) activity in depressive behaviors and suggest that pathways downstream of mTOR complex 1 (mTORC1) may underlie the pathophysiology and treatment of major depressive disorder (Dwyer et al, 2015). These results suggest that fear regulation is mediated by connections from the mPFC to the amygdala, and it seems that mTOR participates in this relationship; in the mPFC, the animals learn to predict aversive events via mTOR, and in the amygdala, the memory is retained
Summary
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that is involved in the control of cell growth and proliferation. This kinase integrates signals triggered by different stimuli such as variations in the amino acid supply, changes in the cellular energy state, and by receptors for various hormones and growth factors and in the brain by transduction of neurotransmitters and neurotrophin signals (Harris and Lawrence, 2003; Gal-Ben-Ari et al, 2012; Burket et al, 2015). Several studies have shown that mTOR participates in multiple functions of the brain. MTOR participates in key processes during neural development, in axon and dendrite development, neuron differentiation, and gliogenesis.
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