Format

Send to

Choose Destination
Biochem Pharmacol. 2018 Nov 9. pii: S0006-2952(18)30453-2. doi: 10.1016/j.bcp.2018.10.026. [Epub ahead of print]

Poly(ADP-ribosylated) proteins in β-amyloid peptide-stimulated microglial cells.

Author information

1
Department of Biochemical Sciences, Sapienza University Roma, Italy.
2
Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine-Temple University, Philadelphia, USA.
3
Department of Biochemical Sciences, Sapienza University Roma, Italy. Electronic address: 3maria.derme@uniroma1.it.

Abstract

Amyloid-treated microglia prime and sustain neuroinflammatory processes in the central nervous system activating different signalling pathways inside the cells. Since a key role for PARP-1 has been demonstrated in inflammation and in neurodegeneration, we investigated PARylated proteins in resting and in β-amyloid peptide treated BV2 microglial cells. A total of 1158 proteins were identified by mass spectrometry with 117 specifically modified in the amyloid-treated cells. Intervention of PARylation on the proteome of microglia showed to be widespread in different cellular districts and to affect various cellular pathways, highlighting the role of this dynamic post-translational modification in cellular regulation. Ubiquitination is one of the more enriched pathways, encompassing PARylated proteins like NEDD4, an E3 ubiquitine ligase and USP10, a de-ubiquitinase, both associated with intracellular responses induced by β-amyloid peptide challenge. PARylation of NEDD4 may be involved in the recruiting of this protein to the plasma membrane where it regulates the endocytosis of AMPA receptors, whereas USP10 may be responsible for the increase of p53 levels in amyloid stimulated microglia. Unfolded protein response and Endoplasmic Reticulum Stress pathways, strictly correlated with the Ubiquitination process, also showed enrichment in PARylated proteins. PARylation may thus represent one of the molecular switches responsible for the transition of microglia towards the inflammatory microglia phenotype, a pivotal player in brain diseases including neurodegenerative processes. The establishment of trials with PARP inhibitors to test their efficacy in the containment of neurodegenerative diseases may be envisaged.

KEYWORDS:

Alzheimer disease; Microglia; PARP-1; Proteomics; β-Amyloid peptide

PMID:
30414941
DOI:
10.1016/j.bcp.2018.10.026

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center