Chemical chaperone therapy, a new strategy for genetic skin fragility disorders.
Chemical chaperone therapy, a new strategy for genetic skin fragility disorders.
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化学伴侣疗法，遗传性皮肤脆弱性疾病的新策略。
DOI：
10.1111/exd.12893
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发表时间：
2016
影响因子：
3.6
通讯作者：
Mukhtar,Hasan
中科院分区：
文献类型：
--
作者：
Chamcheu,JeanChristopher;Siddiqui,ImtiazA;Mukhtar,Hasan
结论目前，对于角蛋白病、果胶病、胶原相关缺陷和其他形式的遗传性皮肤病尚无特异性治疗方法。因此，一些报告评估了化学伴侣的治疗潜力。总而言之，这些数据表明分子伴侣和 MAPK 信号传导的状态对于定义化学或药理学伴侣的机制作用至关重要，并显示出治疗不同遗传性皮肤病理的巨大潜力。然而，如上所述，在解释与已发表的工作相关的矛盾发现时，必须谨慎行事，因为根据不同的因素，可能存在不同的可能情况，包括详细的遗传图谱、疾病表型、存在的其他突变的差异，以及正常和突变蛋白如何分泌及其功能表达。对新分子的严格表征、所涉及的分子机制以及对于减轻脆弱性和维持细胞弹性和组织完整性至关重要的创新机会可能会治愈遗传性皮肤病。至少在 EBS 中，这需要多种动力学，可能包括依赖突变蛋白和天然蛋白的原子分辨率结构模型，同时进行分子对接以及设计可靠的生物标志物
ConclusionCurrently, no specific treatment exists for keratinopathies, plectinopathies, collagen-related defects and other forms of hereditary cutaneous disorders. Therefore, several reports assessed the therapeutic potential of chemical chaperones. Taken together, these data suggest that the status of molecular chaperones and MAPK signalling is critical in defining the mechanistic role of chemical or pharmacological chaperones with demonstrated great potential for treatment of distinct heritable cutaneous pathologies. However, as discussed above, due caution is necessary when interpreting contradictory findings related to published work, as different possible scenarios could exist depending on diverse factors, including differences in detailed genetic profile, disease phenotype, additional mutations present, and how normal and mutant proteins are secreted in conjunction with their functional expression. Rigorous characterization of novel molecules, molecular mechanisms involved and innovative opportunities crucial to alleviate fragility and maintain cell resilience and tissue integrity may remedy genodermatoses. At least in EBS, this requires a variety of dynamics, possibly including reliance on atomic resolution structural model of mutant and native proteins, concomitant to molecular docking as well as devising reliable biomarkers for