Revisiting trypanosomatid nucleoside diphosphate kinases.
Journal
Memorias do Instituto Oswaldo Cruz
ISSN: 1678-8060
Titre abrégé: Mem Inst Oswaldo Cruz
Pays: Brazil
ID NLM: 7502619
Informations de publication
Date de publication:
2022
2022
Historique:
received:
18
10
2021
accepted:
26
11
2021
entrez:
16
2
2022
pubmed:
17
2
2022
medline:
19
2
2022
Statut:
epublish
Résumé
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- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles. 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. The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets. Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets. NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.
Sections du résumé
BACKGROUND
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- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles.
OBJETIVE
OBJECTIVE
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
METHODS
The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets.
FINDINGS
RESULTS
Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets.
MAIN CONCLUSIONS
CONCLUSIONS
NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.
Identifiants
pubmed: 35170678
pii: S0074-02762021000100853
doi: 10.1590/0074-02760210339
pmc: PMC8833001
pii:
doi:
Substances chimiques
Nucleotides
0
Nucleoside-Diphosphate Kinase
EC 2.7.4.6
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e210339Subventions
Organisme : Medical Research Council
ID : MR/P027989/1
Pays : United Kingdom
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