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细胞死亡诱导:通过抑制未折叠蛋白反应(UPR)增强药物毒性。

Cell death induction in : accentuating drug toxicity through inhibition of the unfolded protein response (UPR).

作者信息

Guirao-Abad José P, Weichert Martin, Askew David S

机构信息

Department of Pathology & Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

出版信息

Curr Res Microb Sci. 2022 Feb 18;3:100119. doi: 10.1016/j.crmicr.2022.100119. eCollection 2022.

Abstract

One of the most potent opportunistic fungal pathogens of humans is , an environmental mold that causes a life-threatening pneumonia with a high rate of morbidity and mortality. Despite advances in therapy, issues of drug toxicity and antifungal resistance remain an obstacle to effective therapy. This underscores the need for more information on fungal pathways that could be pharmacologically manipulated to either reduce the viability of the fungus during infection, or to unleash the fungicidal potential of current antifungal drugs. In this review, we summarize the emerging evidence that the ability of to sustain viability during stress relies heavily on an adaptive signaling pathway known as the unfolded protein response (UPR), thereby exposing a vulnerability in this fungus that has strong potential for future therapeutic intervention.

摘要

人类最具致病性的机会性真菌病原体之一是 ,它是一种环境霉菌,可引发具有高发病率和死亡率的危及生命的肺炎。尽管治疗取得了进展,但药物毒性和抗真菌耐药性问题仍然是有效治疗的障碍。这凸显了需要更多关于真菌途径的信息,这些途径可以通过药理学手段进行调控,以降低感染期间真菌的活力,或者释放当前抗真菌药物的杀菌潜力。在本综述中,我们总结了新出现的证据,即 在应激期间维持活力的能力严重依赖于一种称为未折叠蛋白反应(UPR)的适应性信号通路,从而揭示了这种真菌中一个具有强大未来治疗干预潜力的脆弱点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6093/9325865/14b7871685a8/ga1.jpg

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