Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil.
Neurotox Res. 2024 Jun 29;42(4):32. doi: 10.1007/s12640-024-00711-5.
Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the brain. Affected patients usually manifest with neurological symptoms including hypotonia, seizures, epilepsy, lethargy, and coma, the pathophysiology of which is still not completely understood. Treatment is limited and based on lowering Gly levels aiming to reduce overstimulation of N-methyl-D-aspartate (NMDA) receptors. Mounting in vitro and in vivo animal and human evidence have recently suggested that excitotoxicity, oxidative stress, and bioenergetics disruption induced by Gly are relevant mechanisms involved in the neuropathology of NKH. This brief review gives emphasis to the deleterious effects of Gly in the brain of patients and animal models of NKH that may offer perspectives for the development of novel adjuvant treatments for this disorder.
非酮症高甘氨酸血症（NKH）是一种氨基酸代谢遗传疾病，其生化特征为甘氨酸（Gly）在大脑中的蓄积为主。受影响的患者通常表现出神经症状，包括低张力、癫痫发作、癫痫、昏睡和昏迷，其病理生理学尚未完全了解。治疗方法有限，主要是降低 Gly 水平，旨在减少 N-甲基-D-天冬氨酸（NMDA）受体的过度刺激。最近，越来越多的体外和体内动物及人类证据表明，甘氨酸诱导的兴奋性毒性、氧化应激和生物能障碍与 NKH 的神经病理学有关。这篇简要综述强调了 Gly 对 NKH 患者和动物模型大脑的有害影响，这可能为该疾病的新辅助治疗提供了新的视角。
