RESUMO
The cornerstone of antimalarial treatment, artemisinin, has reduced malaria associated morbidity and mortality worldwide. However, Plasmodium falciparum parasites with reduced sensitivity to artemisinin have emerged, and this threatens malaria control and elimination efforts. In this minireview, we describe the initial development of artemisinin as an antimalarial drug, its use both historically and currently, and our current understanding of its mode of action and the mechanisms by which malaria parasites achieve resistance.
Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Resistência a Medicamentos/genética , Humanos , Malária Falciparum/tratamento farmacológico , Mutação , Plasmodium falciparum/genética , Proteínas de Protozoários/genéticaRESUMO
It has been known that osteoclastogenesis is induced by extracellular acidosis-evoked the rise of intracellular calcium ([Ca(2+)]i), which regulate activation of the transcription factor nuclear factor of activated T cells c1 (NFATc1). However, the acid-sensing ion channels (ASICs) involved remain largely unknown. Here, we show that ASIC1a, ASIC1b, ASIC2a, and ASIC3 are expressed in rat osteoclasts, and only ASIC1a is highly upregulated in response to acidosis. Both the ASIC1a-specific blocker PcTX1 and specific siRNA significantly reduce this increase in acid-induced [Ca(2+)]i and acid-induced nuclear translocation of NFATc1, and inhibit acid-induced osteoclast differentiation and bone resorption. These findings show that ASIC1a-mediated calcium entry plays a critical role in osteoclastogenesis by regulating activation of the NFATc1.
