WNTs and their downstream effectors regulate proliferation, death, and migration and cell fate decision. Deregulation of WNT signaling is associated with various cancers including GBM, which is the most malignant primary brain cancer. In this review, we will summarize the experimental evidence supporting oncogenic roles of WNT signaling in GBM and discuss current progress in the targeting of WNT signaling as an anti-cancer approach. In particular, we will focus on (1) genetic and epigenetic alterations that lead to aberrant WNT pathway activation in GBM, (2) WNT-mediated control of GBM stem cell maintenance and invasion, and (3) cross-talk between WNT and other signaling pathways in GBM. We will then review the discovery of agents that can inhibit WNT signaling in preclinical models and the current status of human clinical trials.
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http://dx.doi.org/10.1038/labinvest.2015.140 | DOI Listing |
Front Neurosci
January 2025
Department of Neurophysiology, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico.
The interplay between long-term potentiation (LTP) and epilepsy represents a crucial facet in understanding synaptic plasticity and memory within neuroscience. LTP, a phenomenon characterized by a sustained increase in synaptic strength, is pivotal in learning and memory processes, particularly in the hippocampus. This review delves into the intricate relationship between LTP and epilepsy, exploring how alterations in synaptic plasticity mechanisms akin to those seen in LTP contribute to the hyperexcitable state of epilepsy.
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January 2025
Shaanxi University of Chinese Medicine, Xianyang 712046, China.
Research on bone substitutes for repairing bone defects has drawn increasing attention, and the efficacy of three-dimensional (3D) printed bioactive porous scaffolds for bone defect repair has been well documented. Our previous studies have shown that psoralen can promote osteogenesis by activating the Wnt/β-catenin and BMP/Smad signaling pathways and their crosstalk effects, and psoralen nanospheres have a good osteogenesis-promoting effect with low cytotoxicity. The Chinese medicine oyster shell powder, characterized by its porous structure, strong adsorption, and unique bioactivity, has potential in fracture-promoting repair materials.
View Article and Find Full Text PDFBone Res
January 2025
Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip, osteoporosis and osteoarthritis. Our work addresses the critical question of how these skeletal pathologies emerge. Here, we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Zoology, Aligarh Muslim University, Aligarh 202002, India. Electronic address:
Small molecules are emerging as potential candidates for treating osteoporosis by activating canonical Wnt signaling. These candidates work either by inhibiting DKK-1, sclerostin, SFRP-1, NOTUM, and S1P lyase or by preventing β-catenin degradation through inhibition of GSK-3β, or by targeting Dvl-CXXC5 and axin/β-catenin interactions. While many of these anti-osteoporotic small molecules are in preclinical development, the paucity of FDA-approved small molecules, or promising candidates, that have progressed to clinical trials for treating bone disorders through this mechanism poses a challenge.
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