Neurodegenerative disorders are chronic brain diseases that affect humans worldwide. Although many different factors are thought to be involved in the pathogenesis of these disorders, alterations in several key elements such as the ubiquitin-proteasome system (UPS), the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and the endocannabinoid system (ECS or endocannabinoidome) have been implicated in their etiology. Impairment of these elements has been linked to the origin and progression of neurodegenerative disorders, while their potentiation is thought to promote neuronal survival and overall neuroprotection, as proved with several experimental models. These key neuroprotective pathways can interact and indirectly activate each other. In this review, we summarize the neuroprotective potential of the UPS, ECS, and Nrf2 signaling, both separately and combined, pinpointing their role as a potential therapeutic approach against several hallmarks of neurodegeneration.
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http://dx.doi.org/10.1007/s12640-024-00694-3 | DOI Listing |
Genes Dis
March 2025
Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University, Chongqing 400038, China.
The tumor microenvironment is a complex environment comprising tumor cells, non-tumor cells, and other critical non-cellular components. Some studies about tumor microenvironment have recently achieved remarkable progress in tumor treatment. As a substantial part of post-translational protein modification, ubiquitination is a crucial player in maintaining protein stability in cell signaling, cell growth, and a series of cellular life activities, which are also essential for regulating tumor cells or other non-tumor cells in the tumor microenvironment.
View Article and Find Full Text PDFPhysiol Plant
January 2025
Laboratory of Biotechnology, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poznań, Poland.
Ethylene is an important plant hormone whose production relies on the action of key enzymes, one of which is 1-aminocyclopropane-1-carboxylate synthase (ACS). There are three classes of ACS, which are all partially regulated by degradation through the ubiquitin-proteasome system (UPS), which regulates ethylene production. Arabidopsis has a single class III ACS, ACS7, but although it is known to be degraded by the 26S proteasome, the UPS proteins involved are poorly characterised.
View Article and Find Full Text PDFBioorg Chem
December 2024
Jiangsu Key Laboratory of Drug Design & Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs.
View Article and Find Full Text PDFCurr Protein Pept Sci
January 2025
Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi-75270, Pakistan.
Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.
View Article and Find Full Text PDFACS Chem Biol
January 2025
Institut für Pharmazeutische Chemie, Goethe-University Frankfurt, Biozentrum, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately optimized, both modalities lead to proteasomal degradation of the protein of interest (POI). Due to the complexity of the induced multistep degradation process, controls for degrader evaluation are critical and commonly used in the literature.
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