摘要
HSPB5或者 αB晶状体球蛋白(αBC)是脊椎动物眼球晶状体的主要蛋白,属于蛋白质的小热休克蛋白家族,对各种应激做出反应。αBC也在各种非眼组织的透镜外被发现且充当分子伴侣通过防止蛋白质的聚集,抑制细胞凋亡和炎症。并维持细胞骨架结构。αBC蛋白在三个丝氨酸残基S59、S45 和S19上被磷酸化,且其一些功能也是由磷酸化调控的。大量的研究已经揭示在病理情况下的αBC上调例如神经退行性疾病、癌症、视网膜病变、白内障、缺血/再灌注、老化和其他的病症。然而,αBC的上调对这些病理状况是否具有致病性或是保护性仍未知。虽然αBC已对神经退行性疾病,炎症,糖尿病,和视网膜病变展现出保护作用,其他研究描述了对癌症和肺纤维化的有害作用。αBC单用或与αA晶状体蛋白联用的治疗潜力已经被报道。乙酰αBC肽已被证明比天然的αBC作为分子伴侣更有效,在体内和体外模型的治疗活性均更好。为了使αBC更有效的进入细胞,载体分子如聚乳酸聚乙醇酸共聚物,聚己内酯和细胞穿透肽已被使用。在这篇综述中,我们总结了当前数据,从α BC和BC肽治疗方法的新兴的令人兴奋的研究中和这些蛋白在不同疾病模型中的高效传递方法,包括神经退行性疾病,视网膜病变,血小板聚集,炎症和局部缺血。
关键词: αB晶状体球蛋白,伴侣蛋白,应激,疾病,治疗活性,缩氨酸。
Current Molecular Medicine
Title:Emerging Role for αB-Crystallin as a Therapeutic Agent: Pros and Cons
Volume: 15 Issue: 1
Author(s): V.S. Reddy and G.B. Reddy
Affiliation:
关键词: αB晶状体球蛋白,伴侣蛋白,应激,疾病,治疗活性,缩氨酸。
摘要: HSPB5 or αB-crystallin (αBC) is a major protein of the vertebrate eye lens belonging to the small heat-shock protein family of proteins that respond to various stressful conditions. αBC also is found outside the lens in various non-ocular tissues and acts as a molecular chaperone by preventing aggregation of proteins, inhibits apoptosis and inflammation, and maintains cytoskeletal architecture. The αBC protein is phosphorylated on three serine residues S59, S45, and S19, and several functions of αBC are modulated by phosphorylation. Numerous studies have revealed the upregulation of αBC in pathological conditions such as neurodegenerative diseases, cancers, diabetes, retinal diseases, cataracts, ischemia/repurfusion, aging, and others. However, it is unknown whether the up-regulation of αBC is causative or protective for these pathological conditions. Although αBC has been shown to provide a protective effect in neurodegenerative diseases, inflammation, diabetes, and retinal diseases, other studies have described a deleterious role of αBC in cancers and pulmonary fibrosis. The therapeutic potential of αBC alone or in combination with αA-crystallin has been reported. Acetylated αBC peptides have been shown to be more potent than native αBC for chaperone as well as therapeutic activities using both in vitro and in vivo models. Further, for efficient delivery of α BC into cells, carrier molecules such as polylacticcoglycolic acid, polycaprolactone and cell penetration peptides have been used. In this review, we have summarized current data from emerging and exciting studies of the therapeutic strategies of α BC and α BC peptides and the efficient delivery strategies of these proteins in various disease models, including neurodegenerative diseases, retinal diseases, platelet aggregation, inflammation, and ischemia.
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Cite this article as:
V.S. Reddy and G.B. Reddy , Emerging Role for αB-Crystallin as a Therapeutic Agent: Pros and Cons, Current Molecular Medicine 2015; 15 (1) . https://dx.doi.org/10.2174/1566524015666150114112853
DOI https://dx.doi.org/10.2174/1566524015666150114112853 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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