Abstract.
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.
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Tabaton, M., Tamagno, E. The molecular link between β- and γ-secretase activity on the amyloid β precursor protein. Cell. Mol. Life Sci. 64, 2211–2218 (2007). https://doi.org/10.1007/s00018-007-7219-3
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DOI: https://doi.org/10.1007/s00018-007-7219-3