Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC, Brazil; Department of Basic Sciences of Life, Federal University of Juiz de Fora, 35010-177 Governador Valadares, MG, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jan 10;120:110635. doi: 10.1016/j.pnpbp.2022.110635. Epub 2022 Sep 11.
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.
甲基乙二醛（MGO）是糖酵解的副产物，是一种反应性二羰基化合物。MGO 是高级糖基化终产物（AGEs）的主要细胞通透前体，因为它容易与碱性磷脂和核苷酸以及蛋白质的氨基酸残基（如精氨酸、半胱氨酸和赖氨酸）反应。由 MGO 诱导的 AGEs 的产生与几种病理学广泛相关，包括神经退行性疾病。然而，MGO 代谢和 AGEs 形成在中枢神经系统（特别是神经元、星形胶质细胞和少突胶质细胞）中对行为和精神疾病的影响尚未完全阐明。在这里，我们简要介绍了 MGO 在中枢神经系统中的生物学活性的背景信息。收集了关于 MGO 代谢在生理过程中的作用以及在精神病学神经生物学中的作用的现有信息，特别是与疼痛相关的体验、焦虑、抑郁和认知障碍相关的疾病。为了阐明 MGO 对行为和相关疾病的作用，我们主要回顾了侧重于遗传和药理学方法的临床前研究的主要发现。由于单胺神经递质系统被认为是精神病学和认知相关疾病的病理生理学和治疗的关键靶点，我们还回顾了 MGO 如何影响这些神经递质系统以及这种现象对伤害感受和疼痛、学习和认知、情绪的影响。总之，本综述强调了糖氧酶 1（Glo1）和 MGO 水平在调节行为表型以及相关细胞和分子信号中的关键作用。最后，本综述表明多巴胺是 MGO 的新神经化学靶点，并强调了 MGO 代谢如何调节疼痛、精神和认知相关疾病的病理生理学和治疗。
