Fatima Ghizal, Mahdi Abbas Ali, Alhmadi Hekmat B, Medvedev Oleg
Department of Biotechnology, Era University, Lucknow, India.
Era University, Lucknow, India.
Indian J Clin Biochem. 2025 Oct;40(4):540-550. doi: 10.1007/s12291-024-01278-w. Epub 2024 Nov 11.
Hydrogen sulfide (HS), once recognized as a harmful gas, is now emerging as a very significant biological substance with great emphasis on neuroprotection and neuromodulation. It has several functions within the nervous system, placing its physiological activities, biochemical characteristics as well as therapeutic possibilities to their proper perspective. Endogenously produced by cystathione beta-synthase (CBS), cystathione gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) enzymes, HS is a unique naturally occurring substance that contains multiple biological activities; it is anti-inflammatory, antioxidant, and anti-apoptotic. Such activity allows HS to reduce oxidative stress, which limits mechanisms of cell death and prevents disruption of mitochondria and thus neuronal injury. HS can also be regarded as a neuromodulator because it interacts with and affects the glutamatergic, dopaminergic and GABAergic systems at the synaptic level as well as on neurotransmitter systems and synapse dynamics. It modulates synaptic transmission and its plasticity which is essential for cognitive as well as motor activities and exhibits anti-inflammatory effects which are helpful in the progress of the neurodegenerative condition. Recently gathered some evidence emphasizes as well the possible use of HS in therapeutic interventions in Alzheimer's disease, Parkinson's disease and stroke. In the models of Alzheimer's disease, HS is able to reduce the toxicity of amyloid-beta peptides and improve cognitive performance. In Parkinson's disease, it protects dopaminergic neurons and reduces the severity of motor deficits. Moreover, HS provides protection in ischemic stroke models through decrease of reactive oxygen species and inflammation. Clinical practice with HS-based therapies seems to have certain hurdles even if preclinical results are promising. Aside from stabilizing HS in a biologically active form, developing a delivery system for HS appears a challenge as well. This review will attempt to summarize the existing studies on HS as neuroprotective and neuromodulatory agents, and their avenues of future use and development.
硫化氢（HS）曾被视为有害气体，如今却成为一种极为重要的生物物质，在神经保护和神经调节方面备受关注。它在神经系统中具有多种功能，使其生理活动、生化特性以及治疗潜力得到了恰当的审视。HS由胱硫醚β-合酶（CBS）、胱硫醚γ-裂合酶（CSE）和3-巯基丙酮酸硫转移酶（3-MST）内源性产生，是一种具有多种生物活性的独特天然物质；它具有抗炎、抗氧化和抗凋亡作用。这种活性使HS能够减轻氧化应激，而氧化应激会限制细胞死亡机制并防止线粒体破坏，进而预防神经元损伤。HS也可被视为一种神经调节剂，因为它在突触水平以及神经递质系统和突触动态方面与谷氨酸能、多巴胺能和γ-氨基丁酸能系统相互作用并产生影响。它调节突触传递及其可塑性，而突触传递及其可塑性对于认知和运动活动至关重要，并且具有抗炎作用，有助于神经退行性疾病的进展。最近收集的一些证据也强调了HS在阿尔茨海默病、帕金森病和中风治疗干预中的潜在用途。在阿尔茨海默病模型中，HS能够降低β-淀粉样肽的毒性并改善认知表现。在帕金森病中，它保护多巴胺能神经元并减轻运动缺陷的严重程度。此外，HS通过减少活性氧和炎症在缺血性中风模型中提供保护作用。即使临床前结果很有前景，但基于HS的疗法在临床实践中似乎仍存在一定障碍。除了将HS稳定为生物活性形式外，开发HS的递送系统似乎也是一项挑战。本综述将试图总结关于HS作为神经保护和神经调节剂的现有研究，以及它们未来的使用和发展途径。
