The ubiquitin/proteasome (UP) pathway plays a significant role in many important biological functions and alterations in this pathway have been shown to contribute to the pathology of many human diseases, including cancer. Proteasome inhibition has been well established as a rational strategy for the treatment of multiple myeloma and is currently under investigation for the treatment of other haematological malignancies and solid tumours. Recent evidence suggests that proteasome inhibition may also sensitise tumour cells to the actions of both conventional chemotherapy and radiotherapy, suggesting that this pathway may modify clinical response to anticancer therapy. However, conflicting evidence exists as to the roles of the UP pathway in resistance to treatment. This review endeavours to discuss such roles.
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http://dx.doi.org/10.1016/j.ejca.2007.07.023 | DOI Listing |
Curr 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.
View Article and Find Full Text PDFNeuromolecular Med
January 2025
Department of Rehabilitation Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, No. 168 Gushan Road, Dongshan Street, Jiangning District, Nanjing, 211199, Jiangsu, China.
Muscle atrophy in pathological or diseased muscles arises from an imbalance between protein synthesis and degradation. Elevated levels of interleukin-6 (IL-6) are a hallmark of ischemic stroke and have been associated with muscle atrophy in certain pathological contexts. However, the mechanisms by which IL-6 induces muscle atrophy in the context of stroke remain unclear.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Physiopathology in Aging Laboratory (LIM-22), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
Background: Understanding the molecular mechanisms underlying selective neuronal vulnerability is crucial for developing effective treatments for Alzheimer's disease (AD). Our group has shown that RORB/CDH9-positive excitatory neurons in the entorhinal cortex (EC) display selective vulnerability as early as Braak stage (BB) 2. However, not all RORB/CDH9-positive neurons are vulnerable.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
December 2024
Department of Health, Nutrition, and Food Science, Florida State University, Tallahassee, FL, USA.
Regulation of myocardial mass is key for maintaining cardiovascular health. This review highlights the complex and regulatory relationship between mechanosignaling and myocardial mass, influenced by many internal and external factors including hemodynamic and microgravity, respectively. The heart is a dynamic organ constantly adapting to changes in workload (preload and afterload) and mechanical stress exerted on the myocardium, influencing both physiological adaptations and pathological remodeling.
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