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

@article{MenndezGonzlez2005APPPA,
  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},
  year={2005},
  volume={2},
  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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54 Citations

Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer’s disease
TLDR
The analysis of the lectin binding to sAPPα and sAPPβ suggests that glycosylation dictates the proteolytic pathway for APP processing, which may influence the generation of the different APP fragments and, consequently, the pathological progression of AD.
Effect of APP Isoforms on Cholesterol Metabolism in Alzheimer ’ s Disease
TLDR
It is concluded that a mutation will be needed in APP-KPI(+) in cell model in order to observe significant increase in A β42 formation, cholesterol metabolism and ATP formation when compared to mutated APPKPI(-)-transf ected cell.
APP processing in Alzheimer's disease
TLDR
Current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites are reviewed.
NGF and APP Interplay: Focus on YENPTY Motif of Amyloid Precursor Protein and Y682 Residue
TLDR
A general overview on the current knowledge on NGF and APP interplay is provided, focusing on the events that mediate NGF signalling impairment, and, mostly, on the role of APP Tyrosine 682 phosphorylation whose absence in APPY682G mice impairs APP/TrkA interaction and leads to cholinergicneurodegeneration.
Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities
TLDR
It is concluded that new technologies that reduce the dosage of APP expression may allow disease modification and slow clinical progression, delaying or even preventing onset.
β-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease
TLDR
The biogenesis and toxicity of Aβ as well as the regulation of A β production and clearance are overviewed and current immunotherapeutic approaches targeting Aβ are discussed to give some clues for exploring the more potentially efficient drugs for treatment of AD.
Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.
TLDR
A holistic approach is provided focussing on the effects of isoform-specific RAR modulation with respect to APP secretases and discusses its advantages and drawbacks in subcellular AD related events.
The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides
TLDR
HSP47 is unveiled as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques.
Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death
TLDR
The mechanisms of excessive production of Aβ peptides and APP serving as pathophysiologic stimuli for the initiation of various cell signalling pathways including apoptosis, necrosis, necroptosis and autophagy which lead to neuronal cell death are discussed.
Structural features of the KPI domain control APP dimerization, trafficking, and processing
TLDR
It is shown that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695, and the correlation observed between dimerization, subcellular localization, and processing suggests that dimers acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.
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