Abstract
Mutations in Presenilin-1 (PS1) are the most common cause of early-onset familial Alzheimer’s disease (FAD). Accumulation and deposition of β-amyloid (Aβ) peptides in the cerebral cortex is an early and central process in the pathogenesis of AD. The Aβ peptides are generated from the amyloid precursor protein (APP) as a result of sequential proteolytic cleavages by β3- and y-secretases, which are therefore prime targets for therapeutic intervention. Recent studies showed that Presenilin-1 (PS1) is required for γ-secretase activity and Aβ generation in cultured cells, raising the possibility that targeting PS 1 may be an effective therapeutic strategy for AD 1. Our previous studies of PS1 -/- mice, however, revealed that elimination of PS 1 expression leads to pleiotropic effects during embryonic development, including impaired neurogenesis and reduced Notch signalling2, 3. The perinatal lethality of PS1-/- mice also precluded the investigation of PS 1 function in Aβ generation and amyloid plaque formation in the adult brain where these pathological features develop in AD patients.
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Shen, J. (2002). Presenilin-1 Function in the Adult Brain. In: Mizuno, Y., Fisher, A., Hanin, I. (eds) Mapping the Progress of Alzheimer’s and Parkinson’s Disease. Advances in Behavioral Biology, vol 51. Springer, Boston, MA. https://doi.org/10.1007/978-0-306-47593-1_19
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DOI: https://doi.org/10.1007/978-0-306-47593-1_19
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