APP Processing and the APP-KPI Domain Involvement in the Amyloid Cascade

  title={APP Processing and the APP-KPI Domain Involvement in the Amyloid Cascade},
  author={Manuel Men{\'e}ndez-Gonz{\'a}lez and Pablo P{\'e}rez-Pi{\~n}era and Marta Mart{\'i}nez-Rivera and Mar{\'i}a Teresa Calatayud and B Bl{\'a}zquez Menes},
  journal={Neurodegenerative Diseases},
  pages={277 - 283}
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… 

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Structural features of the KPI domain control APP dimerization, trafficking, and processing

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Findings indicate that although KPI- APP mRNA is abundant in brain, little corresponding protein is present, and KPI+ APP protein (equivalent to protease nexin 2) is the predominant form of APP in human brain.

Glycosylation of the amyloid peptide precursor containing the Kunitz protease inhibitor domain improves the inhibition of trypsin.

Kunitz Protease Inhibitor‐Containing Amyloid β Protein Precursor Immunoreactivity in Alzheimer's Disease

Results suggest that KPI-containing forms of APP are present in dystrophic neurites of senile plaques, and normally in neurons, neuronal processes, and in the vascular compartment in the brain.

Upregulation of amyloid precursor protein isoforms containing Kunitz protease inhibitor in dementia with Lewy bodies.

APP gene family: unique age-associated changes in splicing of Alzheimer's βA4-amyloid protein precursor

Comparison of alternatively spliced APP and APLP2 mRNA isoforms in rat brain regions from early post-natal and adult rats revealed significantly higher relative amounts of KPI-encoding APP iso forms in the adult rat brain and an even more pronounced augmentation of L-APP mRNAs, which indicates an APP-specific age-associated regulation pattern within the APP gene family which has intriguing implications for the development of Alzheimer's disease in humans.

The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II

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Beta-amyloid precursor protein (APP) and APP-RNA are rapidly affected by glutamate in cultured neurons: selective increase of mRNAs encoding a Kunitz protease inhibitor domain.

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Results suggest that the post-translational modification of APP by glycosylation is a key event in determining the processing of the protein.

Cleavage of amyloid beta peptide during constitutive processing of its precursor.

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