Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi, India.
Midnapore Medical College & Hospital, Midnapore, West Bengal, India.
Eur J Pharmacol. 2022 Jun 15;925:174993. doi: 10.1016/j.ejphar.2022.174993. Epub 2022 May 2.
Evidence supports a strong bidirectional association between depression and Type 2 diabetes mellitus (T2DM). The harmful impact of oxidative stress and chronic inflammation on the development of both disorders is widely accepted. Nuclear factor erythroid 2-related factor 2 (NRF2) is a pertinent target in disease management owing to its reputation as the master regulator of antioxidant responses. NRF2 influences the expression of various cytoprotective phase 2 antioxidant genes, which is hampered in both depression and T2DM. Through interaction and crosstalk with several signaling pathways, NRF2 endeavors to contain the widespread oxidative damage and persistent inflammation involved in the pathophysiology of depression and T2DM. NRF2 promotes the neuroprotective and insulin-sensitizing properties of its upstream and downstream targets, thereby interrupting and preventing disease advancement. Standard antidepressant and antidiabetic drugs may be powerful against these disorders, but unfortunately, they come bearing distressing side effects. Therefore, exploiting the therapeutic potential of NRF2 activators presents an exciting opportunity to manage such bidirectional and comorbid conditions.
有证据表明，抑郁症和 2 型糖尿病（T2DM）之间存在强烈的双向关联。氧化应激和慢性炎症对这两种疾病发展的有害影响已被广泛接受。核因子红细胞 2 相关因子 2（NRF2）是疾病管理中的一个重要靶点，因为它是抗氧化反应的主要调节剂。NRF2 影响各种细胞保护相 2 抗氧化基因的表达，而在抑郁症和 T2DM 中，这种表达受到阻碍。通过与几种信号通路的相互作用和串扰，NRF2 努力控制抑郁症和 T2DM 病理生理学中涉及的广泛氧化损伤和持续炎症。NRF2 促进其上游和下游靶标的神经保护和胰岛素增敏特性，从而中断和预防疾病进展。标准的抗抑郁药和糖尿病药物可能对这些疾病有效，但不幸的是，它们伴随着令人痛苦的副作用。因此，利用 NRF2 激活剂的治疗潜力为管理这种双向和共病状态提供了一个令人兴奋的机会。
