is a protozoan parasite of the trypanosomatid family, causing a wide range of diseases with different clinical manifestations including cutaneous, mucocutaneous and visceral leishmaniasis. According to WHO, one billion people are at risk of infection as they live in endemic areas while there are 12 million infected people worldwide. Annually, 0.9-1.6 million new infections are reported and 20-50 thousand deaths occur due to infection. As current chemotherapy for treating leishmaniasis exhibits numerous drawbacks and due to the lack of effective human vaccine, there is an urgent need to develop new antileishmanial therapy treatment. To this end, eukaryotic protein kinases can be ideal target candidates for rational drug design against leishmaniasis. Eukaryotic protein kinases mediate signal transduction through protein phosphorylation and their inhibition is anticipated to be disease modifying as they regulate all essential processes for viability and completion of the parasitic life cycle including cell-cycle progression, differentiation and virulence. This review highlights existing knowledge concerning the exploitation of protein kinases as molecular targets to treat leishmaniasis and the current knowledge of their role in the biology of spp. and in the regulation of signalling events that promote parasite survival in the insect vector or the mammalian host.
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http://dx.doi.org/10.3390/microorganisms9040691 | DOI Listing |
BMC Plant Biol
January 2025
Institute of Food Crops, Hubei Academy of Agricultural Sciences/Key Laboratory of Crop Molecular Breeding, Ministry of Agriculture and Rural Affairs/Hubei Key Laboratory of Food Crop Germplasm and Genetic Improvement, Wuhan, 430064, China.
Background: Sucrose non-fermenting-1-related protein kinases (SnRKs) have been implicated in plant growth and stress responses. Although SnRK3.23 is known to be involved in drought stress, the underlying mechanism of resistance differs between Arabidopsis and rice, and little is known about its function in wheat.
View Article and Find Full Text PDFNat Commun
January 2025
Carisma Therapeutics Inc, Philadelphia, PA, USA.
We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
Osteoarthritis (OA), affecting > 500 million people worldwide, profoundly affects the quality of life and ability to work. The mitogen-activated protein kinase (MAPK) signaling pathway plays an essential role in OA. To address the lack of studies focused on synovial cells in OA, we evaluated the expression patterns and roles of the MAPK signaling pathway components in OA synovial tissues using bioinformatics.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de Montpellier, Montpellier, 34095, France.
Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation.
View Article and Find Full Text PDFT-cell receptor recognition of cognate peptide-MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction.
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