PRIN 2022
"Progetti di Ricerca di Interesse Nazionale"

Obiettivo Principale: Nuovi markers molecolari per le epilessie

DESCRIZIONE

Several studies indicate A Disintegrin And Metalloproteinase 10 (ADAM10) pathway as a new potential therapeutic target in focal epilepsy, whereas, to date, the role of ADAM10 in genetic epilepsy has been poorly investigated. ADAM10 seems to be involved in the neuroinflammation processes underlying the development of epilepsy; however, it remains unclear whether and how ADAM10 modulates neuroinflammation in an epileptic brain or whether ADAM10 affects epileptogenesis via the inflammatory pathway. ADAM10 is also involved in several other neuropsychiatric conditions such as dementia and depression that represent the most frequent comorbidities in patients with epilepsy (PWE). Therefore, we will firstly study the ADAM10 pathway and its involvement in some established hallmarks of the epileptogenic process in two models of epilepsy/epileptogenesis and neuropsychiatric comorbidities: the WAG/Rij rat, a model of genetic epilepsy and the kainate (KA)-induced model of temporal lobe epilepsy (TLE). Besides the brain, ADAM10 is also expressed in the gut, where it is implicated in pathways that regulate gut permeability and inflammation. Hence, we will measure the levels of short-chain fatty acids (SCFAs), inflammation markers and main metabolites. These studies will reveal how ADAM10 pathway is affected and whether it represents a novel therapeutic target in epilepsy-related conditions. We will explore the possibility that several mediators of the ADAM10 pathway may be used as a dynamic biomarker of the aforementioned CNS disorders. Our project will define the involvement and the role of ADAM10 pathway in two different types of epilepsy. Furthermore, the impact of ADAM10 modulators will be evaluated on both seizure and neuropsychiatric comorbidities also in relation to central and peripheral inflammatory pathway modifications. The obtained results might identify new therapeutic targets and biomarkers to study drug effects.

CODICE PROGETTO: 2022879A87

TITOLO PROGETTO: ADAM 10 as a new signaling pathway and target in epilepsy and neuropsychiatric comorbidities: pharmacological modulation in preclinical models

CUP: F53D23006560006

IMPORTO TOTALE DEL PROGETTO: € 373.000,00

IMPORTO FINANZIATO: €107.700,00

FONTE: MUR – PRIN 2022

DATA INIZIO: 20/10/2023

DATA FINE: 28/02/2026

CONTATTI:

follesa@unica.it

biggiof@unica.it