Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
Metab Brain Dis. 2022 Oct;37(7):2181-2195. doi: 10.1007/s11011-022-00956-z. Epub 2022 May 26.
About 50% of the diabetic patients worldwide suffer from Diabetic peripheral neuropathy (DPN) which is characterized by chronic pain and loss of sensation, frequent foot ulcerations, and risk for amputation. Numerous factors like hyperglycemia, oxidative stress (OS), impaired glucose signaling, inflammatory responses, neuronal cell death are known to be the various mechanisms underlying DACD and DPN. Development of tolerance, insufficient and inadequate relief and potential toxicity of classical antinociceptives still remains a challenge in the clinical setting. Therefore, there is an emerging need for novel treatments which are both without any potential side effects as well as which focus more on the pathophysiological mechanisms underlying the disease. Also, sirtuins are known to deacetylate Nrf2 and contribute to its action of reducing ROS by generation of anti-oxidant enzymes. Therefore, targeting sirtuins could be a favourable therapeutic strategy to treat diabetic neuropathy by reducing ROS and thereby alleviating OS in DPN. In the present review, we outline the potential use of SIRT1 activators as therapeutic alternatives in treating DPN. We have tried to highlight how sirtuins are interlinked with Nrf2 and NF-κB and put forth how SIRT activators could serve as potential therapy for DPN.
全球约有 50%的糖尿病患者患有糖尿病周围神经病变（DPN），其特征是慢性疼痛和感觉丧失、频繁的足部溃疡以及截肢风险。高血糖、氧化应激（OS）、葡萄糖信号受损、炎症反应、神经元细胞死亡等众多因素被认为是 DACD 和 DPN 的各种机制。在临床环境中，经典镇痛剂的耐受性发展、缓解不足和潜在毒性仍然是一个挑战。因此，需要新的治疗方法，这些方法既没有任何潜在的副作用，又更侧重于疾病的病理生理机制。此外，Sirtuins 已知可以去乙酰化 Nrf2，并通过生成抗氧化酶来促进其减少 ROS 的作用。因此，通过减少 ROS 从而减轻 DPN 中的 OS，靶向 Sirtuins 可能是治疗糖尿病性神经病的一种有利的治疗策略。在本综述中，我们概述了 SIRT1 激活剂作为治疗 DPN 的治疗替代物的潜在用途。我们试图强调 Sirtuins 如何与 Nrf2 和 NF-κB 相互关联，并提出 SIRT 激活剂如何作为 DPN 的潜在治疗方法。
