Therapeutic potential of α-crystallin

Abstract

Background The findings that α-crystallins are multi-functional proteins with diverse biological functions have generated considerable interest in understanding their role in health and disease. Recent studies have shown that chaperone peptides of α-crystallin could be delivered into cultured cells and in experimental animals with beneficial effects against protein aggregation, oxidation, inflammation and apoptosis. Scope of Review In this review, we will summarize the latest developments on the therapeutic potential of α-crystallins and their functional peptides. Major conclusions α-Crystallins and their functional peptides have shown significant favorable effects against several diseases. Their targeted delivery to tissues would be of great therapeutic benefit. However, α-crystallins can also function as disease-causing proteins. These seemingly contradictory functions must be carefully considered prior to their therapeutic use. General significance αA and αB-Crystallin are members of the small heat shock protein family. These proteins exhibit molecular chaperone and anti-apoptotic activities. The core crystallin domain within these proteins is largely responsible for these prosperities. Recent studies have identified peptides within the crystallin domain of both α- and αB-crystallins with remarkable chaperone and anti-apoptotic activities. Administration of α-crystallin or their functional peptides have shown substantial inhibition of pathologies in several diseases. However, α-crystallins have been shown to promote disease-causing pathways. These two sides of the proteins are discussed in this review.

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

“…αB-crystallin/HspB5 is a widely expressed sHsp first identified in the lens that has been implicated in the pathogenesis of diverse diseases, including myopathies, neurodegenerative disorders, cataracts and cancer (Boelens, 2014). Although there have been several recent reviews highlighting new structural insights and its role in other diseases (Hochberg & Benesch, 2014; Thanos et al, 2014; van der Smagt et al, 2014; Bakthisaran et al, 2015; Haslbeck & Vierling, 2015; Haslbeck et al, 2015; Nagaraj et al, 2015; Treweek et al, 2015), the present review will focus on the mechanisms by which αB-crystallin inhibits cancer cell death, its emerging role as a pathogenic driver in metastasis, and therapeutic efforts to target αB-crystallin in cancer. Insights regarding the role of other sHsps, including Hsp27, in cancer have been reviewed elsewhere (Arrigo et al, 2007; Acunzo et al, 2014).…”

αB-crystallin is essential for the TGF-β2-mediated epithelial to mesenchymal transition of lens epithelial cells

“…αB-Crystallin is also expressed in other tissues such as brain, heart, kidney and skeletal muscles [19]. It is up-regulated in the brain in neurodegenerative diseases, inflammation, breast cancer, retinal diseases and ischaemia/reperfusion injuries (reviewed in [20,21]). Exogenous administration of αB-crystallin has shown beneficial effects against neurological and ocular diseases (reviewed in [20,21]).…”

“…It is up-regulated in the brain in neurodegenerative diseases, inflammation, breast cancer, retinal diseases and ischaemia/reperfusion injuries (reviewed in [20,21]). Exogenous administration of αB-crystallin has shown beneficial effects against neurological and ocular diseases (reviewed in [20,21]). Remarkably, similar beneficial effects have also been observed for a chaperone peptide derived from αB-crystallin [22,23].…”

RNA aptamers targeted for human αA-crystallin do not bind αB-crystallin, and spare the α−crystallin domain

“…These crystallins also play an active role in apoptosis, which seems related to their chaperone activity [5]. Furthermore – based on their apparent role in disease-related processes – sHSPs in general, and α–crystallins in particular, have been associated with exacerbating some diseases while alleviating others [39, 40]. Thus in considering their potential therapeutic role, it is desirable to regulate the functional activity of the α–crystallins positively, as well as negatively.…”