Show pageBacklinksCite current pageExport to PDFBack to top This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong. ====== Hyperphosphorylation ====== **Hyperphosphorylation** is a pathological process in which **excessive phosphate groups** are added to a protein, typically at serine, threonine, or tyrosine residues. It is often due to an **imbalance between kinase and phosphatase activities**. ===== Definition ===== * Abnormal increase in phosphorylation beyond physiological levels. * Leads to altered protein structure, function, and interactions. * Often irreversible in pathological states. ===== Mechanism ===== * Protein kinases (e.g., CDK5, GSK-3β, AMPK) add phosphate groups. * Protein phosphatases (e.g., PP2A) remove them. * In disease states, kinase activity is upregulated or phosphatase activity is suppressed. ===== Pathological Consequences ===== * Protein misfolding * Loss of normal function * Aggregation and toxicity ===== Clinical Relevance ===== ==== Alzheimer’s Disease ==== * **Tau hyperphosphorylation** → detachment from microtubules * Aggregation into **neurofibrillary tangles** * Driven by overactive CDK5, GSK-3β, and suppressed PP2A ==== Cancer ==== * Oncogenic signaling via hyperphosphorylated proteins * Altered control of cell cycle and apoptosis ==== Other Disorders ==== * Parkinson’s disease, frontotemporal dementia, chronic stress response ===== Therapeutic Strategies ===== * **Kinase inhibitors** (e.g., CDK5 or AMPK blockers) * **Phosphatase activators** * **Immunotherapies** targeting hyperphosphorylated epitopes * **Receptor modulation** (e.g., δ-opioid receptor pathways to inhibit tau phosphorylation) ===== Example ===== * Tau → Tau-P → Tau-PP → Tau-PPP → Misfolded/aggregated tau ===== Related Concepts ===== * [[phosphorylation]] * [[tau protein]] * [[CDK5]] * [[neurofibrillary tangles]] * [[kinase]] * [[phosphatase]] hyperphosphorylation.txt Last modified: 2025/07/09 15:48by administrador