Neuronal apoptosis is accompanied by amyloid β-protein accumulation in the endoplasmic reticulum
| Autor: | Paola Strocchi, Roberta Borghi, Alberto Diaspro, Emanuela Lacana, Damiano Zaccheo, Antonella Vitali, Roberta Roncarati, Maria Adelaide Pronzato, Luciano D'Adamio, Luca Pellegrini, Massimo Tabaton |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
Apoptosis Endoplasmic Reticulum Pathogenesis Amyloid beta-Protein Precursor Mice Neuroblastoma Cytosol Tumor Cells Cultured otorhinolaryngologic diseases medicine Animals Humans Staurosporine Caspase Neurons Amyloid beta-Peptides biology Chemistry General Neuroscience Endoplasmic reticulum General Medicine Metabolism Cell biology Psychiatry and Mental health Clinical Psychology Cell culture biology.protein Geriatrics and Gerontology Intracellular medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-2002-4104 |
| Popis: | A series of evidences suggests that enhanced susceptibility to programmed cell death (PCD) is a major pathogenetic factor in Alzheimer's disease (AD). We investigated this issue, analyzing amyloid beta-protein (A beta) production in a model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell line. When PCD was induced, a 280-290% secreted A beta occurred, in spite of a 20% metabolism and an unchanged A betaPP expression. The increased intracellular A beta reactivity largely colocalized with a marker of ER. Inhibition of caspases blocked the cleavage at the C-terminus of beta PP, but only partially rescued A beta overproduction caused by staurosporine treatment. Our findings suggest that PCD fosters the physiological pathways of A beta production characteristic of neuronal cells, and they confirm the theory that unbalance of PCD is a central event in AD pathogenesis. Moreover, our data indicate that still unidentified cellular mechanisms, other than caspases activation, are responsible of the specific alteration of A betaPP processing during PCD. |
| Databáze: | OpenAIRE |
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