Journal
NEURODEGENERATIVE DISEASES
Volume 2, Issue 6, Pages 277-283Publisher
KARGER
DOI: 10.1159/000092315
Keywords
Kunitz protease inhibitor; Amyloid beta precursor protein; Nerve growth factor; Lipoprotein receptor-related protein; Tumor necrosis factor-alpha-converting enzyme; Notch1
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Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor (KPI) domain. KPI is one of the main serine protease inhibitors. Protein and mRNA KPI(+) APP levels are elevated in Alzheimer's disease (AD) brain and are associated with increased amyloid beta deposition. In the last years increasing evidence on multiple points in the amyloid cascade where KPI(+) APP is involved has been accumulated, admitting an outstanding position in the pathogenesis of AD to the KPI domain. This review focuses on the APP processing, the molecular activity of KPI and its physiological and pathological roles and the KPI involvement in the amyloid cascade through the nerve growth factor, the lipoprotein receptor-related protein, the tumor necrosis factor-alpha converting enzyme and the Notch1 protein. Copyright (C) 2005 S. Karger AG, Basel
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