Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, 382355, Gujarat, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, 382355, Gujarat, India.
Neurosci Biobehav Rev. 2017 Dec;83:589-603. doi: 10.1016/j.neubiorev.2017.08.025. Epub 2017 Sep 8.
Disruption of oxidant/anti-oxidant ratio as well as endoplasmic reticulum (ER) stress are thought to be involved in the pathophysiology of schizophrenia. These stresses can lead to impairments in brain functions progressively leading to neuronal inflammation followed by neuronal cell death. Moreover, the cellular stresses are interlinked leading us to the conclusion that protein misfolding, oxidative stress and apoptosis are intricately intertwined events requiring further research into their mechanistic and physiological pathways. These pathways can be targeted by using different therapeutic interventions like anti-oxidants, sigma-1 receptor agonists and gene therapy to treat the neurodegenerative course of schizophrenia. We have also put empahsis on use of synthetic and natural ER stress inhibitors like 4-phenylbutyrate or salubrinal for the treatment of this disorder. This would provide an opportunity to create new therapeutic benchmarks in the field of neuropsychiatric disorders like schizophrenia, dissociative identity disorder and obsessive compulsive disorder.
氧化应激/抗氧化失衡以及内质网（ER）应激被认为与精神分裂症的病理生理学有关。这些应激可导致脑功能逐渐受损，进而导致神经元炎症，随后是神经元细胞死亡。此外，细胞应激相互关联，使我们得出结论，蛋白质错误折叠、氧化应激和细胞凋亡是错综复杂的相互关联的事件，需要进一步研究其机制和生理途径。这些途径可以通过使用不同的治疗干预措施来靶向，如抗氧化剂、西格玛-1 受体激动剂和基因治疗，以治疗精神分裂症的神经退行性过程。我们还强调了使用合成和天然 ER 应激抑制剂，如 4-苯基丁酸或 salubrinal，来治疗这种疾病。这将为精神分裂症、分离性身份障碍和强迫症等神经精神疾病领域创造新的治疗基准提供机会。
