Linking Alzheimer's disease to insulin resistance: the FoxO response to oxidative stress
| Autor: | Peter Korsten, L-O Klotz, Stefan R. Bornstein, Konstantinos N. Manolopoulos, A Barthel |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
endocrine system
medicine.medical_specialty medicine.medical_treatment Biology medicine.disease_cause Models Biological 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Insulin resistance Alzheimer Disease Internal medicine medicine Humans Protein phosphorylation Molecular Biology Transcription factor 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Insulin Neurodegeneration Wnt signaling pathway nutritional and metabolic diseases Forkhead Transcription Factors medicine.disease 3. Good health Cell biology Oxidative Stress Psychiatry and Mental health Endocrinology chemistry Insulin Resistance hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Molecular Psychiatry. 15:1046-1052 |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/mp.2010.17 |
| Popis: | Oxidative stress is an important determinant not only in the pathogenesis of Alzheimer's disease (AD), but also in insulin resistance (InsRes) and diabetic complications. Forkhead box class O (FoxO) transcription factors are involved in both insulin action and the cellular response to oxidative stress, thereby providing a potential integrative link between AD and InsRes. For example, the expression of intra- and extracellular antioxidant enzymes, such as manganese-superoxide dismutase and selenoprotein P, is regulated by FoxO proteins, as is the expression of important hepatic enzymes of gluconeogenesis. Here, we review the molecular mechanisms involved in the pathogenesis of AD and InsRes and discuss the function of FoxO proteins in these processes. Both InsRes and oxidative stress may promote the transcriptional activity of FoxO proteins, resulting in hyperglycaemia and a further increased production of reactive oxygen species (ROS). The consecutive activation of c-Jun N-terminal kinases and inhibition of Wingless (Wnt) signalling may result in the formation of β-amyloid plaques and τ protein phosphorylation. Wnt inhibition may also result in a sustained activation of FoxO proteins with induction of apoptosis and neuronal loss, thereby completing a vicious circle from oxidative stress, InsRes and hyperglycaemia back to the formation of ROS and consecutive neurodegeneration. In view of their central function in this model, FoxO proteins may provide a potential molecular target for the treatment of both InsRes and AD. |
| Databáze: | OpenAIRE |
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