Daniyan Michael Oluwatoyin, Fisusi Funmilola Adesodun, Adeoye Olufunso Bayo
Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
Drug Research and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
Front Mol Biosci. 2022 Aug 24;9:965569. doi: 10.3389/fmolb.2022.965569. eCollection 2022.
is responsible for the most severe and deadliest human malaria infection. The most serious complication of this infection is cerebral malaria. Among the proposed hypotheses that seek to explain the manifestation of the neurological syndrome in cerebral malaria is the vascular occlusion/sequestration/mechanic hypothesis, the cytokine storm or inflammatory theory, or a combination of both. Unfortunately, despite the increasing volume of scientific information on cerebral malaria, our understanding of its pathophysiologic mechanism(s) is still very limited. In a bid to maintain its survival and development, exports a large number of proteins into the cytosol of the infected host red blood cell. Prominent among these are the erythrocytes membrane protein 1 (PfEMP1), histidine-rich protein II (PfHRP2), and heat shock proteins 70-x (PfHsp70-x). Functional activities and interaction of these proteins with one another and with recruited host resident proteins are critical factors in the pathology of malaria in general and cerebral malaria in particular. Furthermore, several neurological impairments, including cognitive, behavioral, and motor dysfunctions, are known to be associated with cerebral malaria. Also, the available evidence has implicated glutamate and glutamatergic pathways, coupled with a resultant alteration in serotonin, dopamine, norepinephrine, and histamine production. While seeking to improve our understanding of the pathophysiology of cerebral malaria, this article seeks to explore the possible links between host/parasite chaperones, and neurotransmitters, in relation to other molecular players in the pathology of cerebral malaria, to explore such links in antimalarial drug discovery.
负责最严重、最致命的人类疟疾感染。这种感染最严重的并发症是脑型疟疾。在试图解释脑型疟疾中神经综合征表现的诸多假说中，有血管阻塞/隔离/机械假说、细胞因子风暴或炎症理论，或两者的结合。不幸的是，尽管关于脑型疟疾的科学信息不断增加，但我们对其病理生理机制的理解仍然非常有限。为了维持其生存和发展，疟原虫向被感染宿主红细胞的细胞质中输出大量蛋白质。其中突出的有红细胞膜蛋白1（PfEMP1）、富含组氨酸蛋白II（PfHRP2）和热休克蛋白70-x（PfHsp70-x）。这些蛋白质彼此之间以及与募集的宿主驻留蛋白的功能活动和相互作用，是一般疟疾尤其是脑型疟疾病理学中的关键因素。此外，已知包括认知、行为和运动功能障碍在内的几种神经损伤与脑型疟疾有关。而且，现有证据表明谷氨酸和谷氨酸能途径，以及血清素、多巴胺、去甲肾上腺素和组胺产生的相应改变。在试图增进我们对脑型疟疾病理生理学理解的同时，本文旨在探讨宿主/寄生虫伴侣蛋白与神经递质之间的可能联系，以及与脑型疟疾病理学中其他分子参与者的关系，以探索抗疟药物发现中的此类联系。
