Phadte Ashutosh S, Sluzala Zachary B, Fort Patrice E
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
Antioxidants (Basel). 2021 Jun 23;10(7):1001. doi: 10.3390/antiox10071001.
The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.
α-晶体蛋白(αA-和αB-)及其衍生物的伴侣蛋白和抗凋亡活性因其在预防细胞死亡方面的巨大潜力而受到越来越多的关注。虽然最初因其在晶状体中的作用而为人所知并被描述,但这些蛋白在神经退行性疾病的细胞和动物模型中的上调突出了它们参与对神经退行性相关应激的适应性保护反应。然而,一些研究也表明,慢性神经退行性疾病与这些蛋白的功能逐渐丧失有关。因此,虽然α-晶体蛋白的外部补充显示出前景,但其作为基于蛋白质的疗法治疗慢性神经退行性疾病的潜力仍不明确。本综述旨在评估支持αA-和αB-晶体蛋白抗凋亡潜力及其在视网膜神经退行性疾病中潜在参与的现有文献。该综述进一步扩展到潜在地调节α-晶体蛋白的伴侣蛋白和抗凋亡功能,以及使用这种功能增强的蛋白来促进视网膜神经退行性疾病中的神经元活力。