O papel dos transportadores de noradrenalina (SLC6A2) no sistema nervoso central

Abstract

The noradrenaline transporters (NETs), part of the SLC6 protein family, play a fundamental role in noradrenergic neurotransmission by reuptaking noradrenaline (NA) released into the synaptic cleft, regulating its concentration and signal duration. These transporters are distributed in strategic regions of the central nervous system (CNS), such as the locus coeruleus, prefrontal cortex, hippocampus, and amygdala, being necessary for processes like attention, memory, mood regulation, and stress response. Additionally, NETs influence cognitive and emotional processes by modulating noradrenaline and dopamine neurotransmission, interacting with dopamine D1 and D2 receptors, especially in the prefrontal cortex. This interaction has significant implications for executive function and emotional balance. This study reviews the literature on the neuroanatomical distribution, intracellular trafficking mechanisms, and functional regulation of NETs, highlighting their modulation through phosphorylation and clathrin-mediated endocytosis. Dysfunctions in these transporters are associated with various pathologies, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and psychiatric disorders such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. The methodological review includes articles published between 1939 and 2024, emphasizing neuroanatomical, physiological, and pharmacological research. Among the therapeutic strategies discussed, selective serotonin and noradrenaline reuptake inhibitors (SSNRIs) have shown efficacy in neurotransmission modulation, reducing psychiatric symptoms. This study reinforces the therapeutic potential of NETs and the need for further investigations to develop more effective interventions for neurological diseases and psychiatric disorders.