Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness
Abdeen S, Salim N, Mammadova N, Summers CM, Goldsmith-Pestana K, McMahon-Pratt D, Schultz PG, Horwich AL, Chapman E, Johnson SM. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness. Bioorganic & Medicinal Chemistry Letters 2016, 26: 5247-5253. PMID: 27720295, DOI: 10.1016/j.bmcl.2016.09.051.Peer-Reviewed Original ResearchConceptsT. brucei infectionBrucei infectionComplex treatment regimensFirst-line drugsNew therapeutic strategiesLeishmania major promastigotesAnti-parasitic potentialTreatment regimensTherapeutic windowTherapeutic strategiesCurrent drugsMajor promastigotesEncouraging initial resultsHuman liverAntibiotic resistanceGreater cytotoxicityProtozoan parasiteKidney cellsMedicinal chemistry optimizationInfectionInhibitorsPotent inhibitorBrucei parasitesDrugsCytotoxicityImmunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model
Siefert AL, Ehrlich A, Corral MJ, Goldsmith-Pestana K, McMahon-Pratt D, Fahmy TM. Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model. Biomaterials 2016, 108: 168-176. PMID: 27636154, PMCID: PMC5049880, DOI: 10.1016/j.biomaterials.2016.09.004.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsAccumulation of MDSCsHyper-inflammatory responseOngoing immune responseCytokine IL-10Antigen-presenting cellsCurrent treatment strategiesInflammation-mediated diseasesLong treatment regimensSite of infectionNew World leishmaniasisCellular immunomodulationIL-17Suppressor cellsDendritic cellsIL-10Immunotherapeutic approachesChronic inflammationTreatment regimensIL-13Free CpGTreatment strategiesTherapeutic effectImmune responsePreclinical studies