Thioredoxin-interacting protein: a potential novel therapeutic target for intervertebral disc degeneration

doi:10.3969/j.issn.1674-8115.2026.05.002

Abstract

Abstract:

The identification of biomarkers is essential for developing innovative therapeutic strategies for intervertebral disc degeneration (IVDD). Thioredoxin-interacting protein (TXNIP), a member of the α-arrestin protein family, is modulated by various cellular stress responses and inhibits the antioxidant activity of thioredoxin through direct binding, thereby promoting oxidative stress. Furthermore, TXNIP interacts with nucleotide-binding domain-like receptor protein 3 (NLRP3) to directly activate inflammatory pathways, playing a pivotal role in IVDD progression. IVDD is a common degenerative disorder closely associated with aging, oxidative stress, and chronic inflammation. Currently, there are no effective drugs to reverse its progression. Recent studies have shown that, in degenerated intervertebral discs, TXNIP expression level is closely associated with inflammatory factors, oxidative damage, and cell death, indicating that TXNIP may serve as a central molecular node linking multiple pathological mechanisms in IVDD. This review systematically elucidates the biological functions of TXNIP in oxidative stress, inflammatory activation, metabolic reprogramming, pyroptosis, and apoptosis, as well as its regulatory networks, and summarizes its pivotal role in the occurrence and development of IVDD. Furthermore, from a translational medicine perspective, this review summarizes the current research progress of therapeutic strategies targeting TXNIP, including small-molecule inhibitors, natural compounds, genetic interventions, and biomaterials, and proposes a multimodal therapeutic pathway and clinical translation direction targeting TXNIP, aiming to provide new insights and theoretical foundations for the mechanistic research and targeted treatment of IVDD.

Key words: thioredoxin-interacting protein (TXNIP), intervertebral disc degeneration (IVDD), targeted therapy

CLC Number:

R681.5⁺3

Liu Yadong, Dong Jinwei, Wang Zihui, Lü Zekun, Ding Baozhi, Ma Hui. Thioredoxin-interacting protein: a potential novel therapeutic target for intervertebral disc degeneration[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(5): 568-575.

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References 67

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