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淀粉样蛋白在疟疾病理生理学中的可能作用。

Possible roles of amyloids in malaria pathophysiology.

作者信息

Moles Ernest, Valle-Delgado Juan José, Urbán Patricia, Azcárate Isabel G, Bautista José M, Selva Javier, Egea Gustavo, Ventura Salvador, Fernàndez-Busquets Xavier

机构信息

Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain; Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain.

Department of Biochemistry & Molecular Biology IV, Universidad Complutense de Madrid, Ciudad Universitaria, ES-28040 Madrid, Spain; Research Institute Hospital 12 de Octubre, Universidad Complutense de Madrid, Ciudad Universitaria, ES-28040 Madrid, Spain; Department of Biochemistry & Molecular Biology IV, Universidad Complutense de Madrid, Ciudad Universitaria, ES-28040 Madrid, Spain; Research Institute Hospital 12 de Octubre, Universidad Complutense de Madrid, Ciudad Universitaria, ES-28040 Madrid, Spain.

出版信息

Future Sci OA. 2015 Sep 1;1(2):FSO43. doi: 10.4155/fso.15.43. eCollection 2015 Sep.

Abstract

The main therapeutic and prophylactic tools against malaria have been locked for more than a century in the classical approaches of using drugs targeting metabolic processes of the causing agent, the protist spp., and of designing vaccines against chosen antigens found on the parasite's surface. Given the extraordinary resources exhibited by to escape these traditional strategies, which have not been able to free humankind from the scourge of malaria despite much effort invested in them, new concepts have to be explored in order to advance toward eradication of the disease. In this context, amyloid-forming proteins and peptides found in the proteome of the pathogen should perhaps cease being regarded as mere anomalous molecules. Their likely functionality in the pathophysiology of calls for attention being paid to them as a possible Achilles' heel of malaria. Here we will give an overview of -encoded amyloid-forming polypeptides as potential therapeutic targets and toxic elements, particularly in relation to cerebral malaria and the blood-brain barrier function. We will also discuss the recent finding that the genome of the parasite contains an astonishingly high proportion of prionogenic domains.

摘要

一个多世纪以来,对抗疟疾的主要治疗和预防手段一直局限于经典方法,即使用针对病原体(原生生物疟原虫属)代谢过程的药物,以及设计针对在寄生虫表面发现的特定抗原的疫苗。鉴于疟原虫展现出非凡的能力来逃避这些传统策略,尽管投入了大量精力,但这些策略仍未能使人类摆脱疟疾的祸害,因此必须探索新的概念,以便朝着根除该疾病迈进。在这种背景下,病原体蛋白质组中发现的形成淀粉样蛋白的蛋白质和肽或许不应再仅仅被视为异常分子。它们在疟原虫病理生理学中的可能功能值得关注,因为这可能是疟疾的一个阿喀琉斯之踵。在此,我们将概述疟原虫编码的形成淀粉样蛋白的多肽作为潜在治疗靶点和毒性元素的情况,特别是与脑型疟疾和血脑屏障功能相关的情况。我们还将讨论最近的一项发现,即疟原虫的基因组包含惊人比例的朊病毒原结构域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3311/5137859/3c1d53067df8/fso-01-43-g1.jpg

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