Abstract
As an ailment, leishmaniasis is still an incessant challenge in neglected tropical diseases and neglected infections of poverty worldwide. At present, the diagnosis and treatment to combat Leishmania tropical infections are not substantial remedies and require advanced & specific research. Therefore, there is a need for a potential novel target to overcome established medicament modalities’ limitations in pathogenicity. In this review, we proposed a few ab initio findings in nucleoporins of nuclear pore complex in Leishmania sp. concerning other infectious protists. So, through structural analysis and dynamics studies, we hypothesize the nuclear pore molecular machinery & functionality. The gatekeepers Nups, export of mRNA, mitotic spindle formation are salient features in cellular mechanics and this is regulated by dynamic nucleoporins. Here, diverse studies suggest that Nup93/NIC96, Nup155/Nup144, Mlp1/Mlp2/Tpr of Leishmania Species can be a picked out marker for diagnostic, immune-modulation, and novel drug targets. In silico prediction of nucleoporin-functional interactors such as NUP54/57, RNA helicase, Ubiquitin-protein ligase, Exportin 1, putative T-lymphocyte triggering factor, and 9 uncharacterized proteins suggest few more noble targets. The novel drug targeting to importins/exportins of Leishmania sp. and defining mechanism of Leptomycin-B, SINE compounds, Curcumins, Selinexor can be an arc-light in therapeutics. The essence of the review in Leishmania’s nucleoporins is to refocus our research on noble molecular targets for tropical therapeutics.
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UniProtKB: https://www.uniprot.org/. USFDA: https://www.fda.gov/. ClinicalTrials: https://clinicaltrials.gov/. StringsDB: https://string-db.org/. InterPro: https://www.ebi.ac.uk/interpro/.
Abbreviations
- NTD:
-
Neglected tropical diseases
- NPC:
-
Nuclear pore complex
- Nup:
-
Nucleoporin
- RNP:
-
Ribonucleoporotein
- FG/GLFG/FXFG:
-
Phenylalanine-glycine/leucine/X-unknown
- VSG:
-
Variant surface glycoprotein
- O-GlcNAc:
-
O-linked GlcNAc transferase
- GlcNAc:
-
N-acetylglucosamine
- NLS/NES:
-
Nuclear localisation signal/nuclear export signal
- RanGDP/GTP:
-
GTP binding; RAs-related nuclear protein
- NTF2:
-
Nuclear transport factor-2
- LMB:
-
Leptomycin B
- SINE:
-
Selective inhibitor of nuclear transport
- rk39:
-
Recombinant kinase 39 amino acids; Anti Leishmania rapid sera diagnosis
- RNAi:
-
RNA interference
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The authors acknowledge the support from NIPER-Hajipur-Vaishali, Bihar, India, and the Indian Council of Medical Research (ICMR-RMRIMS), Patna for providing library facilities.
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AKD contributed to idea generation, conceptualization, and original drafting. PK contributed to technical suggestions. DM and VR did the formal analysis. SKS contributed to reviewing, edited, and correspondence. All authors read and approved the final manuscript.
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Rationale: Leishmaniasis is a clinical challenge for tropical and sub-tropical countries. The limitation in specific diagnostics and therapeutics sparks the researchers to find novel markers that can be highly specific for Leishmania. Nucleoporin review, state-of-the-art will put forth an arc-light in novel tropical therapeutics. Understanding the nucleoporin interacting components of Leishmania sp. and its transport module will provide us with significant architecture and functionality.
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Dubey, A.K., Kumar, P., Mandal, D. et al. An introduction to dynamic nucleoporins in Leishmania species: Novel targets for tropical-therapeutics. J Parasit Dis 46, 1176–1191 (2022). https://doi.org/10.1007/s12639-022-01515-0
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DOI: https://doi.org/10.1007/s12639-022-01515-0