Üremiş Nuray, Üremiş Muhammed Mehdi
Department of Medical Biochemistry, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Turkey.
J Biochem Mol Toxicol. 2025 Jan;39(1):e70133. doi: 10.1002/jbt.70133.
Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression. The heterogeneity of genetic and environmental factors involved in the process of neurodegeneration makes current treatment methods inadequate. However, the existence of common molecular mechanisms in the pathogenesis of these diseases may allow the development of new targeted therapeutic strategies. Oxidative and nitrosative stress damages membrane components by accumulating ROS and RNS and disrupting redox balance. This process results in the induction of apoptosis, which is important in the pathogenesis of neurodegenerative diseases through oxidative stress. Studies conducted using postmortem human samples, animal models, and cell cultures have demonstrated that oxidative stress, nitrosative stress, and apoptosis are crucial factors in the development of diseases such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. The excessive production of reactive oxygen and nitrogen species, elevated levels of free radicals, heightened mitochondrial stress, disturbances in energy metabolism, and the oxidation and nitrosylation of cellular macromolecules are recognized as triggers for neuronal cell death. Challenges in managing and treating neurodegenerative diseases require a better understanding of this field at the molecular level. Therefore, this review elaborates on the molecular mechanisms by which oxidative and nitrosative stress are involved in neuronal apoptosis.
神经退行性疾病是重大的健康问题,对数百万个体的生活质量和寿命有着深远影响。这些疾病的特征是不同脑区的病理变化、与疾病相关的特定基因突变、异常蛋白质沉积以及神经细胞的退化。由于神经退行性疾病在流行病学特征和神经元易损性方面存在差异,这些疾病的治疗通常旨在减缓疾病进展。神经退行性变过程中涉及的遗传和环境因素的异质性使得目前的治疗方法并不完善。然而,这些疾病发病机制中共同分子机制的存在可能有助于开发新的靶向治疗策略。氧化应激和亚硝化应激通过积累活性氧(ROS)和活性氮(RNS)以及破坏氧化还原平衡来损害膜成分。这个过程导致细胞凋亡的诱导,而细胞凋亡通过氧化应激在神经退行性疾病的发病机制中起重要作用。使用人类尸检样本、动物模型和细胞培养进行的研究表明,氧化应激、亚硝化应激和细胞凋亡是阿尔茨海默病、帕金森病、多发性硬化症、肌萎缩侧索硬化症和亨廷顿病等疾病发展的关键因素。活性氧和氮物种的过量产生、自由基水平升高、线粒体应激加剧、能量代谢紊乱以及细胞大分子的氧化和亚硝化被认为是神经元细胞死亡的触发因素。管理和治疗神经退行性疾病面临的挑战需要在分子水平上更好地理解这一领域。因此,本综述阐述了氧化应激和亚硝化应激参与神经元凋亡的分子机制。