Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases

Abstract

Peroxiredoxins (PRDXs) are antioxidant enzymes, known to catalyze peroxide reduction to balance cellular hydrogen peroxide (H2O2) levels, which are essential for cell signaling and metabolism and act as a regulator of redox signaling. Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Early studies demonstrated that PRDXs regulates cell growth, metabolism and immune regulation and therefore involved in the pathologic regulator or protectant of several cancers, neurodegenerative diseases and inflammatory diseases. Oxidative stress and antioxidant systems are important regulators of redox signaling regulated diseases. In addition, thiol-based redox systems through peroxiredoxins have been demonstrated to regulate several redox-dependent process related diseases. In this review article, we will discuss recent findings regarding PRDXs in the development of diseases and further discuss therapeutic approaches targeting PRDXs. Moreover, we will suggest that PRDXs could be targets of several diseases and the therapeutic agents for targeting PRDXs may have potential beneficial effects for the treatment of cancers, neurodegenerative diseases and inflammatory diseases. Future research should open new avenues for the design of novel therapeutic approaches targeting PRDXs.

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

“…PRDXs are also a novel sensitive and highly specific marker for metastatic tumors in in vitro or in vivo models [30]. Previous studies have reported findings in regard to the high expressions of PRDX6 in certain cells, indicating that PRDX6 may be involved in the cancer's development [29]. Based on these reports, this study aimed to survey the effects of PRDX6 expression in tissues on the diagnosis and prognosis in human CRC specimens of positive lymph nodes, which distinguish stage I/II from stage III/VI CRC.…”

“…Recently, peroxiredoxins have an important function in carcinogenesis, suggesting a possible role in cancer cell maintenance. Park et al [29] have demonstrated that the dual action of PRDX6 in tumorigenesis, depending on increased level of PRDX6. We determined that an attempt to identify PRDX6 and validated that the phenotype in CRC is offered by the modulation of PRDX6.…”

“…The present investigation provides a molecular mechanism demonstrating the role of PRDX6 in mediating CRC cancer cell proliferation and migration/invasion. PRDX6 overexpression in many human cancers, serving a potential prognostic marker, regulated cell-cycle regulatory proteins and its transcriptional induction by oxidative stress via increased activity of redoxsensitive transcription factors and activation of PI3K/AKT/p38/p50 signaling pathways, which are able to interact with the PRDX6 gene promoter region and/or increased oncogenic activity present in cancer cells leading to cancer progression [29,34,44,34]. These data suggest that the levels of PRDX6 and Nox1 components are closely linked positively regulates NADPH oxidase Noxa1 activity involved in superoxide generation (Fig.…”

“…3A). PRDX6, is highly expressed in cancer cells and transcriptionally regulated by various oxidative stresses and signaling regulators [29]. PRDX6 plays an important role in the oxidative stress response, as an anti-apoptotic function, and then loss of Prdx6 increases susceptibility to oxidative stress [30].…”

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

“…In addition, qPCR analysis of several fetal myeloid cell markers, namely Tal1 (Kelliher et al, 1996), Klf1 (McConnell and Yang, 2010) and Prdx3 (Park et al, 2016), revealed a tendency for an increase in their expression levels in the Sox17 +/− gallbladder region, together with a positive correlation among these three genes ( Fig. S6A,B).…”