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The S100A4 protein signals through the ErbB4 receptor to promote neuronal survival.

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Title: The S100A4 protein signals through the ErbB4 receptor to promote neuronal survival.
Authors: Kiryushko, D
Pankratova, S
Klingelhofer, J
Dmytriyeva, O
Owczarek, S
Renziehausen, A
Syed, N
Porter, A
Dexter, D
Kiryushko, D
Item Type: Journal Article
Abstract: Understanding the mechanisms of neurodegeneration is crucial for development of therapies to treat neurological disorders. S100 proteins are extensively expressed in the injured brain but S100's role and signalling in neural cells remain elusive. We recently demonstrated that the S100A4 protein protects neurons in brain injury and designed S100A4-derived peptides mimicking its beneficial effects. Here we show that neuroprotection by S100A4 involves the growth factor family receptor ErbB4 and its ligand Neuregulin 1 (NRG), key regulators of neuronal plasticity and implicated in multiple brain pathologies. The neuroprotective effect of S100A4 depends on ErbB4 expression and the ErbB4 signalling partners ErbB2/Akt, and is reduced by functional blockade of NRG/ErbB4 in cell models of neurodegeneration. We also detect binding of S100A4 with ErbB1 (EGFR) and ErbB3. S100A4-derived peptides interact with, and signal through ErbB, are neuroprotective in primary and immortalized dopaminergic neurons, and do not affect cell proliferation/motility - features which make them promising as potential neuroprotectants. Our data suggest that the S100- ErbB axis may be an important mechanism regulating neuronal survival and plasticity
Issue Date: 1-Jul-2018
Date of Acceptance: 10-Apr-2018
URI: http://hdl.handle.net/10044/1/60422
DOI: https://dx.doi.org/10.7150/thno.22274
ISSN: 1838-7640
Publisher: Ivyspring International Publisher
Start Page: 3977
End Page: 3990
Journal / Book Title: Theranostics
Volume: 8
Issue: 14
Copyright Statement: © The authors. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Sponsor/Funder: Commission of the European Communities
Brain Tumour Research Campaign
Brain Tumour Research Campaign
Barrow Foundation UK
Brain Tumour Research Campaign
Funder's Grant Number: PIEF-GA-2013-627049
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Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
S100
S100A4
ErbB
neuroprotection
peptide
LONG-TERM POTENTIATION
CENTRAL-NERVOUS-SYSTEM
SILICA NANOPARTICLES
DOPAMINERGIC-NEURONS
HIPPOCAMPAL-NEURONS
CEREBRAL-CORTEX
UP-REGULATION
BRAIN-INJURY
TYROSINE KINASE
NMDA RECEPTOR
ErbB
S100
S100A4
neuroprotection
peptide
Publication Status: Published
Online Publication Date: 2018-07-01
Appears in Collections:Materials
Physics
Experimental Solid State
Department of Brain Sciences
Faculty of Natural Sciences
Faculty of Engineering