鉴于H2S在脑功能中的重要作用,有人提出,H2S也可能对神经毒物的不利影响具有保护作用。因此,本综述的目的是讨论H2S对神经系统疾病发病机制中涉及的多种内源性和外源性药物的毒性的神经保护作用,这些药物是疾病发病机制中的病因或关键参与者。一般来说,现有数据表明,H2S在暴露于内源性(β淀粉样蛋白,葡萄糖,和晚期糖基化终产物,同型半胱氨酸,脂多糖,和氨)和外源性(酒精,甲醛,丙烯腈,金属,6-羟基多巴胺,以及1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)及其代谢物1-甲基-4-苯基吡啶离子(MPP))神经毒物。一方面,神经保护作用是由抗氧化剂(Sirt1,Nrf2)和炎症反应(NF-κB)的关键调节剂的S-硫酸盐介导的,导致下行信令的调制,如SIRT1/TORC1/CREB/BDNF-TrkB,Nrf2/ARE/HO-1或其他途径。另一方面,H2S似乎通过结合内源性(ROS,AGEs,Aβ)和外源性(MeHg)神经毒物,从而降低其毒性。此外,通过抑制大脑中的H2S合成酶来改变H2S代谢(CBS,3-MST)可能被认为是神经毒性的重要机制。一起来看,现有数据表明,脑H2S代谢的调节可用作神经保护策略,以抵消与神经变性(阿尔茨海默氏病和帕金森氏病)相关的多种内源性和外源性神经毒物的神经毒性。胎儿酒精综合症,肝性脑病,环境神经毒物暴露,等。在这种特殊情况下,调节H2S合成酶或使用H2S释放药物应被视为潜在的工具,尽管此类干预措施的特定效率和安全性有待进一步研究。
In view of the significant role of H2S in brain functioning, it is proposed that H2S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H2S against toxicity of a wide spectrum of endogenous and exogenous agents involved in the pathogenesis of neurological diseases as etiological factors or key players in disease pathogenesis. Generally, the existing data demonstrate that H2S possesses neuroprotective effects upon exposure to endogenous (amyloid β, glucose, and advanced-glycation end-products, homocysteine, lipopolysaccharide, and ammonia) and exogenous (alcohol, formaldehyde, acrylonitrile, metals, 6-hydroxydopamine, as well as 1-methyl-4-phenyl- 1,2,3,6- tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenyl pyridine ion (MPP)) neurotoxicants. On the one hand, neuroprotective effects are mediated by S-sulfhydration of key regulators of antioxidant (Sirt1, Nrf2) and inflammatory response (NF-κB), resulting in the modulation of the downstream signaling, such as SIRT1/TORC1/CREB/BDNF-TrkB, Nrf2/ARE/HO-1, or other pathways. On the other hand, H2S appears to possess a direct detoxicative effect by binding endogenous (ROS, AGEs, Aβ) and exogenous (MeHg) neurotoxicants, thus reducing their toxicity. Moreover, the alteration of H2S metabolism through the inhibition of H2S-synthetizing enzymes in the brain (CBS, 3-MST) may be considered a significant mechanism of neurotoxicity. Taken together, the existing data indicate that the modulation of cerebral H2S metabolism may be used as a neuroprotective strategy to counteract neurotoxicity of a wide spectrum of endogenous and exogenous neurotoxicants associated with neurodegeneration (Alzheimer\'s and Parkinson\'s disease), fetal alcohol syndrome, hepatic encephalopathy, environmental neurotoxicant exposure, etc. In this particular case, modulation of H2S-synthetizing enzymes or the use of H2S-releasing drugs should be considered as the potential tools, although the particular efficiency and safety of such interventions are to be addressed in further studies.