Peroxisome proliferator-activated receptor-γ (PPARγ) is a critical regulator of adipogenesis and bone metabolism, playing complex roles in osteoporosis. This study investigates the effects of taurine and homocysteine on PPARγ, focusing on their roles in osteoclastogenesis and bone health. In-silico analyses, including molecular docking and molecular dynamic simulations, revealed that both taurine and homocysteine bind competitively to the PPARγ ligand-binding domain, exhibiting distinctive antagonistic modes, including destabilization of PPARγ's key helices H3, H4/5, H11, and H12.
View Article and Find Full Text PDFSclerostin (SOST), a Wnt signaling pathway inhibitor, is involved in the pathogenesis of skeletal disorders. This study investigated the impact of the GKWWRPS motif on the PNAIG motif in Loop 2 of SOST, which is accountable for the interactions with the LRP6 protein that triggers the down-regulation of the Wnt signaling pathway. Single amino acid mutations on the GKWWRPS motif, hypothesized to have a probable stabilization effect towards the PNAIG motif, led to a significant reduction in the primary interactions between the SOST and LRP6 proteins.
View Article and Find Full Text PDFIn the last few decades, the rates of infertility among women have been on the rise, usually due to complications with the uterus and related tissue. A wide variety of reasons can cause uterine factor infertility and can be congenital or a result of disease. Uterine transplantation is currently used as a means to enable women with fertility issues to have a natural birth.
View Article and Find Full Text PDFThe cysteine-knot containing negative regulator of the Wnt (Wingless-related integration site) signaling pathway, sclerostin (SOST) is an emerging therapeutic target for osteoporosis. Its inhibition is responsible for the promotion of osteoblastogenesis. In this study, taurine, an amino sulfonic acid was used to study its mechanism of action for the inhibition of the SOST protein.
View Article and Find Full Text PDFUnderstanding the detailed mechanism behind every human disease, disorder, defect, and deficiency is a daunting task concerning the clinical diagnostic tools for patients. Hence, a closely resembling living or simulated model is of paramount interest for the development and testing of a probable novel drug for rectifying the conditions pertaining to the various ailments. The animal model that can be easily genetically manipulated to suit the study of the therapeutic motive is an indispensable asset and within the last few decades, the zebrafish models have proven their effectiveness by becoming such potent human disease models with their use being extended to various avenues of research to understand the underlying mechanisms of the diseases.
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