SGK1 regulates stress, cancer, heart, brain, and cell survival functions ? скачать в хорошем качестве

SGK1 regulates stress, cancer, heart, brain, and cell survival functions ?

SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) is a serine/threonine protein kinase that plays a critical role in cellular responses to stress, the regulation of ion channels and transporters, hormone release, cell survival, proliferation, apoptosis, and other physiological processes����.Basic FunctionSGK1 is rapidly upregulated by various stimuli, including serum, glucocorticoids, insulin, growth factors, and cellular stress��. It is activated through a signaling cascade involving PI3K, PDK1, and mTORC2��.Key Roles and ProcessesIon Channel and Transporter Regulation: SGK1 enhances the activity and stability of several sodium, potassium, and chloride channels, as well as various membrane transporters (such as glucose transporters, creatine transporter, and Na+/K+-ATPase), which are essential for maintaining cellular homeostasis���.Cell Survival and Apoptosis: It inhibits apoptosis, in part by phosphorylating forkhead transcription factors (like FOXO3a), and has antiapoptotic effects that support cell viability���.Proliferation and Stress Response: SGK1 expression is upregulated in response to cellular stress, mediating cell proliferation and tissue repair, and supporting glucose uptake and energy supply during low-energy states��.Neuronal and Systemic Effects: SGK1 regulates neuroexcitability, memory, renal sodium/potassium balance, salt appetite, and blood pressure sensitivity, influencing both the nervous and cardiovascular systems���.Transcriptional Regulation: It interacts with and regulates the activity of several transcription factors (CREB, AP-1, NF-κB, β-catenin, p53) as well as enzymes like GSK3A/B and PMM2��.Clinical ImportanceDisease Associations: SGK1 dysregulation is implicated in hypertension, metabolic disorders, neurodegenerative diseases, and certain heart and kidney conditions��.Therapeutic Potential: Because SGK1 orchestrates responses to stress and cell survival, it is under investigation as a target for therapies against cardiovascular, renal, metabolic, and neurological diseases��.Mechanisms of ActionSGK1 contributes to the regulation of epithelial sodium channels (ENaC) by inhibiting their degradation (via phosphorylation of NEDD4L) and increasing their expression, a mechanism crucial for sodium reabsorption in the kidney�.It modulates store-operated calcium entry (SOCE), cardiac potassium and sodium channels, and impacts cellular energy supply by stimulating glycolysis and angiogenesis��.In skeletal muscle, SGK1 helps maintain muscle mass under stress conditions by inhibiting autophagy and atrophy via the suppression of Foxo3a�.In summary, SGK1 is a central signaling kinase that integrates stress signals and regulates key functions across multiple tissues, making it essential for cellular adaptability and systemic physiological homeostasis���. Recent research on SGK1 (serum- and glucocorticoid-regulated kinase 1) has significantly broadened understanding of its functions and disease associations. New studies reveal that SGK1 is heavily involved in cancer biology, cardiovascular and neurological diseases, and stress responses�������.SGK1 and CancerSGK1 has emerged as both a powerful diagnostic and prognostic biomarker in various cancers. It promotes tumor proliferation, invasion, metastasis, and resistance to therapy. High SGK1 expression is linked to poor prognosis in cancers such as non-small cell lung cancer and esophageal squamous cell carcinoma. Inhibiting SGK1 leads to cancer cell apoptosis and reduced metastasis, and new inhibitors are under research for targeted therapies�.Cardiovascular and COVID-19 LinksSGK1 regulates ionic balance and affects cardiac sodium channels, influencing conditions like atrial fibrillation (AF) and contributing to arrhythmia risk. During COVID-19, SGK1 was shown to worsen inflammation and lung injury by modulating the cytokine storm. Targeting SGK1 may therefore help manage both cardiac and COVID-19-related complications�.Neurological and Psychiatric FindingsSGK1 plays an important role in neurodegenerative diseases and depression. Elevated SGK1 levels in the brain are associated with stress, early life adversity, trauma, and increased vulnerability to depression and suicidal behavior����. Recent work shows that blocking SGK1 activity can prevent stress-induced depressive behaviors in animal models�. SGK1 also emerges as a therapeutic target for neuroprotection, with the development of brain-penetrant inhibitors��.New SGK1 InhibitorsUnlike previous years, novel, brain-permeable SGK1 inhibitors are under active development, opening therapeutic possibilities for both neurological and oncological applications. Early studies report favorable safety profiles in animal models, encouraging further drug development��. #viral #education #science #2025 #2026 #upsc #viral #viralvideo #education