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

Regulation and Implication

Sanaz Nasoohi, Saifudeen Ismael, Tauheed Ishrat

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Neurological 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 stress 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 metabolism. Recently, a significant body of literature has supported an essential role of TXNIP in the activation of the NOD-like receptor protein (NLRP3)-inflammasome, a well-established multi-molecular protein complex and a pivotal mediator of sterile inflammation. Accordingly, TXNIP has been postulated to reside centrally in detecting cellular damage and mediating inflammatory responses to tissue injury. The majority of recent studies have shown that pharmacological inhibition or genetic deletion of TXNIP is neuroprotective and able to reduce detrimental aspects of pathology following cerebrovascular and neurodegenerative diseases. Conspicuously, the mainstream of the emerging evidences is highlighting TXNIP link to damaging signals in endothelial cells. Thereby, here, we keep the trend to present the accumulative data on CNS diseases dealing with vascular integrity. This review aims to summarize evidence supporting the significant contribution of regulatory mechanisms of TXNIP with the development of brain diseases, explore pharmacological strategies of targeting TXNIP, and outline obstacles to be considered for efficient clinical translation.

Original languageEnglish (US)
Pages (from-to)7900-7920
Number of pages21
JournalMolecular Neurobiology
Volume55
Issue number10
DOIs
StatePublished - Oct 1 2018

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Cerebrovascular Disorders
Thioredoxins
Neurodegenerative Diseases
Proteins
Brain Diseases
Glucose
Stroke
Pharmacology
Pathology
Inflammasomes
Inflammation
Inflammation Mediators
Central Nervous System Diseases
Acute Disease
Psychological Stress
Sulfhydryl Compounds
Oxidation-Reduction
Blood Vessels
Alzheimer Disease
Oxidative Stress

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases : Regulation and Implication. / Nasoohi, Sanaz; Ismael, Saifudeen; Ishrat, Tauheed.

In: Molecular Neurobiology, Vol. 55, No. 10, 01.10.2018, p. 7900-7920.

Research output: Contribution to journalReview article

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