αB-crystallin as a promising target in pathological conditions – A review

Abstract

Introduction and objective. αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. State of knowledge. α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. Conclusions. Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.

The Transglutaminase-2 Interactome in the APP23 Mouse Model of Alzheimer’s Disease

“…Alike TG2, 14-3-3 protein plays a role in cell survival and the autophagy pathway and both their expression is altered in AD, suggesting a possible connection to neurodegeneration in AD [43,47]. Our findings also hint towards an Aβdriven process in which TG2 crosslinks alpha-B-crystallin, thereby modifying Aβ-induced cytotoxicity, as suggested previously [44,45], or hampering alpha-B-crystallin physiological functioning in recognizing misfolded proteins [48]. In addition, amongst the TG2 interactors common for APP23 and WT is the well-known AD risk factor and key player in both Aβ-pathophysiology and AD-related neurodegeneration [49,50], Apolipoprotein E (ApoE), which we recently identified as a substrate for TG2-catalyzed crosslinking [21].…”

Resolution Potential of Necrotic Cell Death Pathways

“…In vivo αBcrystallin protected retinal ganglion cells against ischemia/reperfusion [26] and attenuated the inflammatory response in injured spinal cords [27] and experimental autoimmune encephalomyelitis [28]. The immunosuppressive function of αB-crystallin is also supported by its tumor-promoting role, although whether this is due to its extracellular or intracellular functions has not been investigated [29,30]. As with HSP27, αB-crystallin is upregulated during stress conditions [24], and may also be secreted by cells via exosome production [31].…”

Small Heat Shock Proteins in Retinal Diseases

“…HspB1, B5, and B6 have been shown to regulate angiogenesis ( Dimberg et al, 2008 ; Lee et al, 2012 ; Zhang et al, 2012 ; Tao et al, 2019 ), associated with tumor progression and neovascularization in retinal diseases. Several reports are available about the promotion of epithelial to mesenchymal transition in various cells/tissues by HspB1 and B5, which is a phenomenon that supports malignant cell metastasis ( Shiota et al, 2013 ; Cordonnier et al, 2015 ; Shi et al, 2017a ; Li et al, 2017 ; Chen et al, 2018a ; Han et al, 2018 ; Maksimiuk et al, 2020 ).…”