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Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
The P's and Q's of cellular PrP-Aβ interactions
David Westaway1, Jack H Jhamandas
1Department of Medicine (Neurology), University of Alberta, Edmonton, AB Canada. david.westaway@ualberta.ca
Prion
|August 10, 2012
Summary
Prion disease research reveals shared mechanisms with Alzheimer's disease (AD), including protein misfolding and "seeded spread" of aggregates. These findings suggest common pathways in neurodegeneration, impacting AD and prion disease understanding.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Prion diseases involve protein misfolding, converting alpha-helical PrP(C) to beta-sheet PrP(Sc).
- Alzheimer's disease (AD) involves beta-amyloid (Aβ) peptide misfolding from APP.
- Early hypotheses of overlap were overshadowed by prion disease transmission controversies.
Purpose of the Study:
- To explore surprising mechanistic overlaps between prion diseases and Alzheimer's disease.
- To review contemporary literature identifying commonalities in neurodegenerative pathways.
- To focus on the role of PrP(C) in these shared mechanisms.
Main Methods:
- Review of contemporary literature on prion diseases and AD.
- Analysis of "seeded spread" phenomena for Aβ, Tau, and α-synuclein.
- Investigation of PrP(C) interactions with Aβ and APP processing.
Main Results:
- Prion and AD share "seeded spread" of misfolded protein aggregates.
- Pathologic Aβ effects can be mediated by binding to PrP(C).
- Similarities exist in PrP(C) and APP processing pathways and cellular environments (lipid rafts).
- Overlapping protein interactomes (interactomes) are observed between PrP(C) and APP.
- Rare cases show mixed AD and prion pathologies.
Conclusions:
- Despite initial differences, prion research offers concrete mechanistic insights into AD.
- Shared pathways involving protein misfolding, seeded spread, and cellular machinery are evident.
- Further research into these commonalities can advance understanding and treatment of both prion diseases and AD.
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