Amyloid-β₄₂ activates the expression of BACE1 through the JNK pathway
| Autor: | Guglielmotto, M, Monteleone, D, Giliberto, L, Fornaro, M, Borghi, Roberta, Tamagno, E, Tabaton, Massimo |
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| Přispěvatelé: | Guglielmotto, Michela, Monteleone, Debora, Giliberto, Luca, Fornaro, Michele, Borghi, Roberta, Tamagno, Elena, Tabaton, Massimo |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Amyloid beta-Peptide MAP Kinase Signaling System Enzyme-Linked Immunosorbent Assay Mice Transgenic Transfection Amyloid beta-Protein Precursor Mice Neuroblastoma Peptide Fragment Cell Line Tumor Animals Aspartic Acid Endopeptidases Humans Aspartic Acid Endopeptidase Enzyme Inhibitor Amyloid Precursor Protein Secretase Enzyme Inhibitors Analysis of Variance Amyloid beta-Peptides Animal Brain Peptide Fragments Mice Inbred C57BL Gene Expression Regulation Mutation Amyloid Precursor Protein Secretases Human |
| Popis: | The sequential endoproteolytic cleavages operated by the γ-secretase and the β-secretase (BACE1) on the amyloid-β protein precursor (AβPP) result in the production of the amyloid-β (Aβ) species, with two C-terminal variants, at residue 40 or at residue 42. Accumulation in brain tissue of small, soluble aggregates of Aβ42 is the major pathogenic event of Alzheimer's disease (AD). However, the physiologic activity of Aβ peptides is still elusive. Here, we show that expression of BACE1 is regulated by Aβ42, which augments BACE1 gene transcription through the JNK/c-jun signaling pathway. Of note, Aβ40 has much less effect on BACE1 expression. These findings unveil a positive feedback loop in which γ-secretase cleavage of AβPP releases a functionally-active peptide, Aβ42, that promotes BACE1 transcription. Thus, gene expression induced by Aβ42 may have implications in the neuronal dysfunction and degeneration that occurs in AD. |
| Databáze: | OpenAIRE |
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