Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

Abstract

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

A 6-CpG validated methylation risk score model for metabolic syndrome: The HyperGEN and GOLDN studies

“…Independent CpGs included were cg00574958 from carnitine palmitoyl transferase 1A ( CPT1A) , cg02650017 from Phosphoethanolamine/Phosphocholine Phosphatase 1 ( PHOSPHO1 ), cg06500161 from ATP Binding Cassette Subfamily G Member 1 ( ABCG1 ), cg11024682 from Sterol Regulatory Element Binding Transcription Factor 1 ( SREBF1 ), cg18181703 from Suppressor Of Cytokine Signaling 3 ( SOCS3 ), and cg19693031 from Thioredoxin Interacting Protein ( TXNIP ). Bolstering to the validity of our CpG selection each gene has strong biological plausibility for association with MetS including roles in fatty acid metabolism ( CPT1A ) [ 17 ], lipid homeostasis and metabolism ( SREBF1 [ 18 ], ABCG1 ) [ 19 ], skeletal endocrine regulation of metabolism ( PHOSPHO1 ) [ 20 ], cytokine signaling (SOCS3) [ 21 ] and oxidative stress ( TXNIP ) [ 22 ].…”

Tanshinol Alleviates Microcirculation Disturbance and Impaired Bone Formation by Attenuating TXNIP Signaling in GIO Rats

“…TXNIP has attracted considerable attention regarding drug development owing to its multiple functions and involvement in metabolic disorders, inflammation, neurodegenerative disorders as well as cancer ( Qayyum et al, 2021 ). Generally, TXNIP is considered as a vital regulator in response to oxidative stress relying on interacting with reduced thioredoxin (Trx),and further blocking its potential for scavenging reactive oxygen species ( Alhawiti et al, 2017 ).…”

“…Our previous evidence further revealed that TXNIP elicited bone loss by promoting the excessive mitochondrial oxidative phosphorylation under conditions of oxidative stress induced by GC, which can be blocked in the TXNIP knockout mice ( Mo et al, 2021 ). Several preclinical and clinical evidence related to diabetes mellitus supported the TXNIP-specific inhibitors for the development of new promising agents ( Qayyum et al, 2021 ), such as Verapamil ( Khodneva et al, 2016 ), Taurine ( Gondo et al, 2012 ), and SRI-37330 ( Thielen et al, 2020 ). It was reported that TXNIP pathway could be inhibited by a salvianolate injection ( Qiu et al, 2018 ), the main water-soluble bioactive compounds of Salvia miltiorrhiza bunge.…”

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris

“…TXNIP increases reactive oxygen species production by binding with thioredoxin. TXNIP is upregulated in diabetes, cardiovascular disease, and neurodegerative disorders [81]. PTN expression can be triggered in tissues by many factors including inflammation and mechanical stress [82].…”