The expanding impact of methylglyoxal on behavior-related disorders.

Methylglyoxal (MGO) is a reactive dicarbonyl compound formed as a byproduct of glycolysis. MGO is a major cell-permeant precursor of advanced glycation end products (AGEs), since it readily reacts with basic phospholipids and nucleotides, as well as amino acid residues of proteins, such as arginine, cysteine, and lysine. The AGEs production induced by MGO are widely associated with several pathologies, including neurodegenerative diseases. However, the impact of MGO metabolism and AGEs formation in the central nervous system (particularly in neurons, astrocytes and oligodendrocytes) on behavior and psychiatric diseases is not fully understood. Here, we briefly present background information on the biological activity of MGO in the central nervous system. It was gathered the available information on the role of MGO metabolism at the physiological processes, as well as at the neurobiology of psychiatry diseases, especially pain-related experiences, anxiety, depression, and cognition impairment-associated diseases. To clarify the role of MGO on behavior and associated diseases, we reviewed primarily the main findings at preclinical studies focusing on genetic and pharmacological approaches. Since monoamine neurotransmitter systems are implicated as pivotal targets on the pathophysiology and treatment of psychiatry and cognitive-related diseases, we also reviewed how MGO affects these neurotransmission systems and the implications of this phenomenon for nociception and pain; learning and cognition; and mood. In summary, this review highlights the pivotal role of glyoxalase 1 (Glo1) and MGO levels in modulating behavioral phenotypes, as well as related cellular and molecular signaling. Conclusively, this review signals dopamine as a new neurochemical MGO target, as well as highlights how MGO metabolism can modulate the pathophysiology and treatment of pain, psychiatric and cognitive-related diseases.