Efstathiou Antonia, Smirlis Despina
Microbiology Department, Hellenic Pasteur Institute, Avenue Vas. Sofias 127, 11521 Athina, Greece.
Microorganisms. 2021 Mar 27;9(4):691. doi: 10.3390/microorganisms9040691.
is a protozoan parasite of the trypanosomatid family, causing a wide range of diseases with different clinical manifestations including cutaneous, mucocutaneous and visceral leishmaniasis. According to WHO, one billion people are at risk of infection as they live in endemic areas while there are 12 million infected people worldwide. Annually, 0.9-1.6 million new infections are reported and 20-50 thousand deaths occur due to infection. As current chemotherapy for treating leishmaniasis exhibits numerous drawbacks and due to the lack of effective human vaccine, there is an urgent need to develop new antileishmanial therapy treatment. To this end, eukaryotic protein kinases can be ideal target candidates for rational drug design against leishmaniasis. Eukaryotic protein kinases mediate signal transduction through protein phosphorylation and their inhibition is anticipated to be disease modifying as they regulate all essential processes for viability and completion of the parasitic life cycle including cell-cycle progression, differentiation and virulence. This review highlights existing knowledge concerning the exploitation of protein kinases as molecular targets to treat leishmaniasis and the current knowledge of their role in the biology of spp. and in the regulation of signalling events that promote parasite survival in the insect vector or the mammalian host.
是锥虫科的一种原生动物寄生虫，可引发多种具有不同临床表现的疾病，包括皮肤利什曼病、黏膜皮肤利什曼病和内脏利什曼病。据世界卫生组织称，有10亿人因生活在流行地区而面临感染风险，而全球有1200万感染者。每年报告的新感染病例为90万至160万，因感染导致2万至5万人死亡。由于目前治疗利什曼病的化疗存在诸多缺点，且缺乏有效的人类疫苗，因此迫切需要开发新的抗利什曼病治疗方法。为此，真核蛋白激酶可能是针对利什曼病进行合理药物设计的理想靶点。真核蛋白激酶通过蛋白质磷酸化介导信号转导，预计抑制它们可改变疾病，因为它们调节寄生虫生存和完成寄生生命周期的所有基本过程，包括细胞周期进程、分化和毒力。本综述重点介绍了有关将蛋白激酶作为治疗利什曼病的分子靶点的现有知识，以及目前对其在利什曼原虫生物学中的作用以及在促进寄生虫在昆虫媒介或哺乳动物宿主中存活的信号事件调节中的作用的认识。
