Abstract
Phosphoinositide 3-kinase (PI3K) signaling contributes to a variety of processes, mediating many aspects of cellular function, including nutrient uptake, anabolic reactions, cell growth, proliferation, and survival. Less is known regarding its critical role in neuronal physiology, neuronal metabolism, tissue homeostasis, and the control of gene expression in the central nervous system in healthy and diseased states. The aim of the present work is to review cumulative evidence regarding the participation of PI3K pathways in neuronal function, focusing on their role in neuronal metabolism and transcriptional regulation of genes involved in neuronal maintenance and plasticity or on the expression of pathological hallmarks associated with neurodegeneration.
Highlights
Phosphoinositide 3-kinases (PI3Ks) are a family of multifaceted enzymes that play a central role in diverse metabolic processes that regulate many aspects of cell physiology
Less is known regarding its critical role in neuronal physiology, neuronal metabolism, tissue homeostasis, and the control of gene expression in the central nervous system in healthy and diseased states
The aim of the present work is to review cumulative evidence regarding the participation of PI3K pathways in neuronal function, focusing on their role in neuronal metabolism and transcriptional regulation of genes involved in neuronal maintenance and plasticity or on the expression of pathological hallmarks associated with neurodegeneration
Summary
Phosphoinositide 3-kinases (PI3Ks) are a family of multifaceted enzymes that play a central role in diverse metabolic processes that regulate many aspects of cell physiology. In the brain regions aforementioned, activation of the AKT/mTOR pathway seems to be essential for neuronal development and synapse formation [11,12,13,14] and contributes to neuronal plasticity and memory performance [15,16,17,18]. The activation of this pathway through receptor tyrosine kinase (RTK) by growth factors constitute the core path that regulates neuronal proliferation, maturation, and integration into mature circuits in the brain [19]. The important function of PI3K in neurons has been demonstrated for its involvement in severe brain pathologies, such as developmentally-associated brain malformations [20,21], epilepsy [22,23], aging-associated neurodegeneration [24,25,26], and brain cancer [27,28]
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