The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights

Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and is recognized as a major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, and therapeutic strategies for IDD are currently limited. Oxidative stress plays pivotal roles in the pathogenesis and progression of many age-related diseases in humans, including IDD. Nuclear factor E2-related factor 2 (Nrf2) is a master antioxidant transcription factor that protects cells against oxidative stress damage. Nrf2 is negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) and exerts important effects on IDD progression. Accumulating evidence has revealed that Nrf2 can facilitate the transcription of downstream antioxidant genes in disc cells by binding to antioxidant response elements (AREs) in promoter regions, including heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and NADPH quinone dehydrogenase 1 (NQO1). The Nrf2 antioxidant defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, the inflammatory response of the nucleus pulposus (NP), and calcification of the cartilaginous endplates (EP) in IDD. In this review, we aim to discuss the current knowledge on the roles of Nrf2 in IDD systematically. Intervertebral disc degeneration: Boosting regulatory protein may enhance treatment Insights into the activity of a protein that regulates gene expression and protects cells against oxidative stress could yield novel treatments for lower back pain. Intervertebral disc degeneration (IDD) is a common cause of lower back pain, but the molecular mechanisms underlying IDD are unclear, meaning treatment options are limited. Oxidative stress is implicated in IDD, and scientists have begun exploring the role of nuclear factor E2-related factor 2 (Nrf2), a master regulator of the body's antioxidant responses, in regulating IDD progression. In a review of recent research, Weishi Li at Peking University Third Hospital, Beijing, China, and co-workers point out that boosting the activity of Nrf2-related signaling pathways alleviates oxidative stress in intervertebral disc cells. The researchers suggest that therapies based on non-coding RNAs may prove valuable in activating Nrf2 in IDD patients.

Automated summary

Intervertebral disc degeneration (IDD) is a common cause of lower back pain, and the molecular mechanisms underlying IDD are unclear, limiting treatment options. Oxidative stress is implicated in IDD, and the regulatory protein nuclear factor E2-related factor 2 (Nrf2) has been found to play a role in regulating IDD progression. Boosting Nrf2 activity through non-coding RNA therapies may be a valuable approach to alleviate oxidative stress in intervertebral disc cells.