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Differential pattern of neurotoxicity induced by the gliadin peptides p31-43 and p57-68 in in vitro model of epilepsy.
Gerace, Elisabetta; Resta, Francesco; Curti, Lorenzo; Di Domizio, Alessandro; Ranieri, Giuseppe; Becatti, Matteo; Renzi, Daniela; Calabrò, Antonino; Mannaioni, Guido.
Afiliación
  • Gerace E; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Italy; Department of Health Sciences (DSS), University of Florence, Florence, Italy. Electronic address: elisabetta.gerace@unifi.it.
  • Resta F; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Italy.
  • Curti L; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Italy.
  • Di Domizio A; SPILLOproject, Milano, Italy.
  • Ranieri G; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Italy.
  • Becatti M; Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Firenze, Italy.
  • Renzi D; Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Firenze, Italy.
  • Calabrò A; Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Firenze, Italy.
  • Mannaioni G; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Italy.
Biochem Pharmacol ; 226: 116409, 2024 08.
Article en En | MEDLINE | ID: mdl-38969300
ABSTRACT
Epilepsy is a central nervous system (CNS) disorder causing repeated seizures due to a transient excessive or synchronous alteration in the electrical activity of the brain. Several neurological disorders have been associated to gluten-related diseases (GRD), including epilepsy. However, the molecular mechanisms that associate GRD and epileptogenesis are still unknown. Our previous data have shown that the gliadin peptide 31-43 (p31-43) enhanced number and duration of seizures induced by kainate in mice and exacerbated CA3-kainate-induced neurotoxicity in organotypic hippocampal slices. Here, we investigated whether another important gliadin peptide p57-68 may exerts effects similar to p31-43 on kainate-induced neurotoxicity. We find that both peptides exacerbate kainate-induced damage in the CA3 region once simultaneously challenged. However, after pre-incubation, p31-43 additionally exacerbates neurotoxicity in the CA1 region, while p57-68 does not. These data suggested differential intracellular mechanisms activated by the peptides. Indeed, analysing intracellular signalling pathways we discover that p31-43 induces significant intracellular changes, including increased phosphorylation of Akt, Erk1/2, and p65, decreased p38 phosphorylation, and deacetylation of nuclear histone-3. Based on these observations, we demonstrate that p31-43 likely activates specific intracellular signaling pathways involved in neuronal excitability, inflammation, and epigenetic regulation, which may contribute to its exacerbation of kainate-induced neurotoxicity. In contrast, p57-68 appears to exert its effects through different mechanisms. Further research is necessary to elucidate the precise mechanisms by which these peptides influence neurotoxicity and understand their implications for neurological disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Epilepsia / Gliadina Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Epilepsia / Gliadina Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido