Revisiting trypanosomatid Nucleoside Diphosphate Kinases

MIRANDA, MARIANA; SAYE, MELISA; REIGADA, CHANTAL; GALCERAN, FACUNDO; RENGIFO, MARCOS; MACIEL, BELEN; DIGIROLAMO FABIO; PEREIRA, CA

MEMóRIAS DO INSTITUTO OSWALDO CRUZ.

FUNDACO OSWALDO CRUZ

Año: 2022

0074-0276

BACKGROUND An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK)as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di- and tri- phosphatenucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signaltransduction and many other regulatory roles.OBJETIVE Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g.,Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention.METHODS The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features,multifunctionality and suitability as molecular drug targets.FINDINGS Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that theywould perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responsesand gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractivepharmacological targets.MAIN CONCLUSIONS NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatidNDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.