Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication

AbstractNeurological diseases, including acute attacks (e.g., ischemic stroke) and chronic neurodegenerative diseases (e.g., Alzheimer ’s disease), have always been one of the leading cause of morbidity and mortality worldwide. These debilitating diseases represent an enormous disease burden, not only in terms of health suffering but also in economic costs. Although the clinical presentations differ for these diseases, a growing body of evidence suggests that oxidative stress and inflammatory responses in brain tissue significantly contribute to their pathology. However, therapies attempting to prevent oxidative damage or inhibiting inflammation have shown little success. Identification and targeting endogenous “upstream” mediators that normalize such processes will lead to improve therapeutic strategy of these diseases. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the thioredoxin (TRX) system, a major cellular thiol-reducing and antioxidant system. TXNIP regulating redox/glucose-induced str ess and inflammation, now is known to get upregulated in stroke and other brain diseases, and represents a promising therapeutic target. In particular, there is growing evidence that glucose strongly induces TXNIP in multiple cell types, suggesting possible physiological roles of TXNIP in glucose me tabolism. Recently, a significant body of literature has supported an essential role of TXNIP in the activation of the NOD-like receptor protein (NLRP3)-inflamma...

Source: Molecular Neurobiology - February 27, 2018 Category: Neurology Source Type: research