Rana Ravi, Mukherjee Ritam, Mehan Sidharth, Khan Zuber, Das Gupta Ghanshyam, Narula Acharan S
Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India; Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab 144603, India.
Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India; Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab 144603, India.
Behav Brain Res. 2025 May 8;485:115545. doi: 10.1016/j.bbr.2025.115545. Epub 2025 Mar 20.
Neurological disorders significantly impair neuronal function and lead to cognitive and motor deficits. This review manuscript explores the therapeutic potential of key proteins-Klotho, SIRT-1, Nrf2, and HO-1-in combating these disorders. Neurological conditions encompass neurotraumatic, neurodegenerative, and neuropsychiatric diseases, all characterized by neuronal loss and dysfunction. The complex functions of Klotho, an anti-aging protein, and SIRT-1, a histone deacetylase, highlight their roles in neuronal survival and neuroprotection through the enhancement of antioxidant defences and the modulation of stress responses. Nrf2 functions as the principal regulator of the antioxidant response, whereas HO-1 facilitates the control of oxidative stress and the resolution of inflammation. Evidence suggests that the interplay between these proteins facilitates neuroprotection by decreasing oxidative damage and promoting cognitive function. The study emphasises the significance of signalling pathways, particularly the Nrf2/HO-1 axis, which are essential in mitigating oxidative stress and inflammation linked to neurodegenerative disorders. Future therapeutic strategies must consider personalized approaches, innovative drug delivery systems, and early intervention to optimize outcomes. This review provides a comprehensive framework for understanding how targeting these pathways can mitigate the burden of neurological disorders, advancing the development of effective interventions for enhancing brain health.
神经系统疾病会显著损害神经元功能，并导致认知和运动功能障碍。这篇综述文章探讨了关键蛋白——α-klotho、沉默信息调节因子1（SIRT-1）、核因子E2相关因子2（Nrf2）和血红素加氧酶1（HO-1）——在对抗这些疾病方面的治疗潜力。神经系统疾病包括神经创伤性、神经退行性和神经精神性疾病，其特征均为神经元丢失和功能障碍。抗衰老蛋白α-klotho和组蛋白去乙酰化酶SIRT-1的复杂功能，凸显了它们通过增强抗氧化防御和调节应激反应在神经元存活和神经保护中的作用。Nrf2作为抗氧化反应的主要调节因子发挥作用，而HO-1则有助于控制氧化应激和炎症消退。有证据表明，这些蛋白之间的相互作用通过减少氧化损伤和促进认知功能来实现神经保护。该研究强调了信号通路的重要性，特别是Nrf2/HO-1轴，其在减轻与神经退行性疾病相关的氧化应激和炎症方面至关重要。未来的治疗策略必须考虑个性化方法、创新的药物递送系统和早期干预，以优化治疗效果。这篇综述提供了一个全面的框架，用于理解靶向这些通路如何减轻神经系统疾病的负担，推动开发增强脑健康的有效干预措施。
