Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

The S100A4 Protein Signals through the ErbB4 Receptor to Promote Neuronal Survival

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. In vivo characterization of a novel norepinephrine transporter PET tracer [18F]NS12137 in adult and immature Sprague-Dawley rats

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Remote loading of liposomes with a 124I-radioiodinated compound and their in vivo evaluation by PET/CT in a murine tumor model

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Simultaneous characterization of tumor cellularity and the Warburg effect with PET, MRI and hyperpolarized 13C-MRSI

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. First-in-human uPAR PET: Imaging of Cancer Aggressiveness

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial metabolites

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 "Signalosome"

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalTheranostics
Volume8
Issue number14
Pages (from-to)3977-3990
Number of pages14
ISSN1838-7640
DOIs
Publication statusPublished - 2018

ID: 54923932