Vol. 123, No. 1 (Supplement) 2018
Supplement abstract

Molecular mechanism of PACAP-induced EGFR transactivation in an in vitro model of ALS

PDF
  • Grazia Maugeri,
  • Agata Grazia D’Amico2,
  • Daniela Maria Rasà,
  • Concetta Federico,
  • Salvatore Saccone,
  • Sebastiano Cavallaro,
  • Velia D’Agata
Grazia Maugeri
University of Catania, Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, Catania
Agata Grazia D’Amico2
University of Rome, San Raffaele Open University of Rome, Department of Human Science and Promotion of quality of Life, Roma
Daniela Maria Rasà
University of Catania, Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, Catania
Concetta Federico
University of Catania, Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, Catania
Salvatore Saccone
University of Catania, Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, Catania
Sebastiano Cavallaro
National Research Council, Institute of Neurological Sciences, Catania
Velia D’Agata
University of Catania, Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, Catania
DOI: https://doi.org/10.13128/ijae-11455

Published 2018-12-30

Keywords

  • ALS,
  • PACAP,
  • EGFR,
  • MMP-2

How to Cite

Maugeri, G., D’Amico2, A. G., Rasà, D. M., Federico, C., Saccone, S., Cavallaro, S., & D’Agata, V. (2018). Molecular mechanism of PACAP-induced EGFR transactivation in an in vitro model of ALS. Italian Journal of Anatomy and Embryology, 123(1), 144. https://doi.org/10.13128/ijae-11455
Copyright Notice

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting both upper and lower motor neurons. By analyzing the transcriptional profile of motor cortex samples from sporadic ALS (SALS) patients, we have previously selected two patient subgroups, known as SALS1 and SALS2. Since Cu/Zn-superoxide dismutase-1 (SOD1) mutation is involved some cases of familial ALS, we have also compared the gene expression profile of motor cortex from SALS patients and SOD1 G93A mice through a meta-analysis study [1]. From this analysis, 19 statistically significant genes emerged as deregulated both in mice and SALS patients, com- prising: pituitary adenylate cyclase-activating polypeptide (PACAP), epidermal growth factor receptor (EGFR) and matrix metallopeptidase 2 (MMP-2) [2]. Considering the functional link between PACAP and EGFR, already described both in neurons and in cancer cells, here we have investigated the involvement of PACAP, EGFR and MMP-2 genes in this neurodegenera- tive disease.

The study has been performed in NSC34 motor neuronal cell lines expressing G93A SOD1.

Our data have showed that PACAP is able to rescue cells degeneration following growth factors deprivation. Its effect is induced through EGFR transactivation mediated by protein kinase A stimulation. Moreover, EGFR phosphorylation triggers the activation of MEK/ERK1/2 survival signaling pathway and increased MMP-2 expression, drastically reduced by serum starvation.

In conclusion, our findings suggest that a deeply characterization of the mechanism linking PACAP/EGFR/MMP-2 axis to SOD1 mutation may open a new perspective for ALS therapy.

PDF

Metrics

Metrics Loading ...

Most read articles by the same author(s)

1 2 3 > >>