The molecular link between β- and γ-secretase activity on the amyloid β precursor protein
| Autor: | M. Tabaton, E. Tamagno |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Pharmacology
biology Chemistry Amyloid beta P3 peptide Cell Biology Presenilin Cell biology Cellular and Molecular Neuroscience Alpha secretase Biochemistry mental disorders biology.protein Amyloid precursor protein Molecular Medicine APH-1 Molecular Biology Amyloid precursor protein secretase Gamma secretase |
| Zdroj: | Cellular and Molecular Life Sciences. 64:2211-2218 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-007-7219-3 |
| Popis: | Alzheimer’s disease (AD) is characterized by an accumulation in the brain of amyloid β peptides (Aβ). The production of Aβ requires two sequential cleavages induced by β- and γ-secretases on the β-amyloid precursor protein (APP). Altered activity of these secretases is involved in the pathogenesis of AD. The expression and activity of β-secretase (BACE1) is augmented in the brain in late-onset sporadic AD. Mutant presenilin 1 (PS1), the major genetic defect of early-onset familial AD (FAD), alters the activity of γ-secretase, leading to increased production of Aβ42. Here we review the role of oxidative stress as a molecular link between the β- and the γ-secretase activities, and provide a mechanistic explanation of the pathogenesis of sporadic late-onset AD. We also discuss evidence for a role of the same mechanism in the pathogenesis of familial AD carrying PS1 mutations. |
| Databáze: | OpenAIRE |
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