title: Acetylation and phosphorylation of STAT3 are involved in the responsiveness of microglia to beta amyloid.
abstract: Microglia are macrophages within the central nervous system playing a central role in neurodegenerative disorders. Although the initial engagement of microglia seems to be neuroprotective, many lines of evidence indicate that its persistent activation contributes to dismantle neuronal activity and to induce neuronal loss. The molecular pathways that lead from amyloid interaction with membrane receptors to the microglial activation have been extensively investigated, although a definitive picture is not yet at hand. In this work, primary and immortalized microglial cells were treated with a synthetic form of Aβ peptides, and relative abundance of acetylated and phosphorylated STAT3 were assayed. Results highlight, for the first time, three distinctive sequential events: i) an earlier event marked by the increase in the level of STAT3 acetylated species, followed by ii) a later increase in the level of STAT3 phosphorylated form, and finally iii) an involvement of phosphorylated STAT3 in the increase in expression of the 14-3-3 epsilon, a protein frequently associated with neurodegenerative diseases and known to be a marker of Aβ-activated microglia. These data outline a complex, time-dependent modification of STAT3 signalling triggered by amyloid in the microglial compartments, that once confirmed by in vivo experiments will broaden the knowledge of the molecular basis of amyloid neurotoxicity.
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy.
authors: Margherita
authors: M
authors: Eufemi
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy.
authors: Rossana
authors: R
authors: Cocchiola
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy.
authors: Donatella
authors: D
authors: Romaniello
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy.
authors: Virginia
authors: V
authors: Correani
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy.
authors: Laura
authors: L
authors: Di Francesco
authors: Dipartimento di Scienze Anatomiche, Istologiche, Medico-Legali e dell'Apparato Locomotore, Sapienza, University of Rome, Via Borelli, 50 00161 Rome, Italy.
authors: Cinzia
authors: C
authors: Fabrizi
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy.
authors: Bruno
authors: B
authors: Maras
authors: Dipartimento di Scienze Biochimiche, Sapienza, University of Rome, P.le Aldo Moro, 5 00185 Rome, Italy. Electronic address: eugenia.schinina@uniroma1.it.
authors: M Eugenia
authors: ME
authors: Schininà
mesh_terms: D000107:Acetylation; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: 14-3-3epsilon; Alzheimer's disease; Amyloid beta peptides; Microglia; STAT3