HIF-1α downregulates the APP protein after oxygen and glucose deprivation in the APPswe/PSEN1 mouse model of Alzheimer’s disease
The mTORC1 and AMPK signalling pathways are considered key nodes regulating anabolism and catabolism, and they are altered in certain processes of neurodegeneration such as hypoxia associated with ischemic stroke or Alzheimer's disease. The lack of oxygen and/or glucose (oxygen and glucose depr...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/397984 |
| Acceso en línea: | http://hdl.handle.net/10261/397984 |
| Access Level: | acceso abierto |
| Palabra clave: | mTORC1 AMPK, autophagy APPAmyloid-β hypoxia Alzheimer's disease OGD Neurodegeneration and neurons |
| Sumario: | The mTORC1 and AMPK signalling pathways are considered key nodes regulating anabolism and catabolism, and they are altered in certain processes of neurodegeneration such as hypoxia associated with ischemic stroke or Alzheimer's disease. The lack of oxygen and/or glucose (oxygen and glucose deprivation-OGD) may affect the equilibrium of the mTORC1/AMPK pathways, perhaps aggravating neurodegeneration. The alteration of these pathways mediated by OGD may be reflected in other alterations, such as the activation of autophagy that could in turn modify the secretion/accumulation of amyloid-β, one of the two histopathological markers of Alzheimer's disease. Accordingly, we set out to analyze whether OGD enhances autophagy and its implication in neuronal amyloidosis. The data obtained reveal that OGD significantly dampens not only neuronal amyloid-β production but also, the total APP protein levels, without affecting BACE-1 levels. We show that this mechanism is independent of cellular proteolysis (autophagy or proteasome) and that it can be partially recovered by inhibiting HIF-1α activity. |
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