PUBLICATION
Uncontrolled SFK-mediated protein trafficking in prion and Alzheimer's disease
- Authors
- Málaga-Trillo, E., Ochs, K.
- ID
- ZDB-PUB-160923-13
- Date
- 2016
- Source
- Prion 10(5): 352-361 (Review)
- Registered Authors
- Málaga-Trillo, Edward
- Keywords
- Alzheimer's disease, Aβ peptide, E-cadherin, NMDA receptor, Prion protein, Src family kinases, endocytosis, neurotransmission, synaptic damage, zebrafish
- MeSH Terms
-
- Alzheimer Disease/enzymology
- Alzheimer Disease/metabolism*
- Alzheimer Disease/therapy
- Amyloid beta-Peptides/metabolism
- Animals
- Cadherins/metabolism
- Endocytosis
- Humans
- Mice
- Prion Diseases/enzymology
- Prion Diseases/metabolism*
- Prion Diseases/therapy
- Protein Transport
- Signal Transduction
- src-Family Kinases/metabolism*
- PubMed
- 27649856 Full text @ Prion
Citation
Málaga-Trillo, E., Ochs, K. (2016) Uncontrolled SFK-mediated protein trafficking in prion and Alzheimer's disease. Prion. 10(5):352-361.
Abstract
Prions and Amyloid beta (Aβ) peptides induce synaptic damage via complex mechanisms that include the pathological alteration of intracellular signaling cascades. The host-encoded cellular prion protein (PrPC) acts as a high-affinity cell surface receptor for both toxic species and it can modulate the endocytic trafficking of the N-methyl D-aspartate (NMDA) receptor and E-cadherin adhesive complexes via Src family kinases (SFKs). Interestingly, SFK-mediated control of endocytosis is a widespread mechanism used to regulate the activity of important transmembrane proteins, including neuroreceptors for major excitatory and inhibitory neurotransmitters. Here we discuss our recent work in zebrafish and accumulating evidence suggesting that subversion of this pleiotropic regulatory mechanism by Aβ oligomers and prions explains diverse neurotransmission deficits observed in human patients and mouse models of prion and Alzheimer's neurodegeneration. While Aβ, PrPC and SFKs constitute potential therapeutic targets on their own, drug discovery efforts might benefit significantly from aiming at protein-protein interactions that modulate the endocytosis of specific SFK targets.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping