Descrizione del progetto
Lo stress ossidativo e i percorsi correlati all’invecchiamento come bersagli per la prevenzione del morbo di Parkinson
Il morbo di Parkinson è il secondo disturbo neurodegenerativo più comune e, secondo le stime, colpisce l’1 % della popolazione mondiale con più di 60 anni. Gli attivatori patogenetici del morbo di Parkinson sono per lo più sconosciuti e gli attuali trattamenti alleviano i sintomi solo parzialmente senza ripristinare la normale funzione neuronale. Il progetto PARNANT, finanziato dall’UE, sfrutterà l’esperienza dei partner nella genetica di Caenorhabditis elegans e nei modelli di morbo di Parkinson basati sulle cellule per trovare i percorsi genetici che mediano la protezione contro la neurodegenerazione durante lo stress ossidativo e l’invecchiamento. Studi precedenti hanno identificato 51 loci genetici candidati associati alla neurodegenerazione correlata all’età nei modelli di morbo di Parkinson e nei relativi pazienti. I ricercatori si propongono di intervenire su questi geni per alleviare lo stress ossidativo nei neuroni dopaminergici e proteggerli contro la degenerazione.
Obiettivo
Parkinson’s disease (PD) is the second most common neurodegenerative disorder (after Alzheimer's) associated with oxidative stress and aging, and affects an estimated 1% of people worldwide over 60 years of age. The pathogenetic triggers of neurodegenerations are largely unknown. Current therapeutic interventions only partially alleviate symptoms and do not restore normal neuronal function or prevent progressive neurodegenerations. Identifying novel molecular targets and searching for therapeutic agents that block neurodegeneration and promote neuronal restoration is a key challenge in the field. I and the Host have together identified 51 candidate genetic loci associated with age-related neurodegenerations in PD model and PD patients, respectively. These candidate genes are evolutionarily conserved in both vertebrate and invertebrate animals. I hypothesize that some of these genes, via an evolutionarily conserved signal transduction pathway, alleviate the oxidative stress in the dopaminergic neurons and protect them against degeneration. This project combines my (C. elegans genetics) and Host (cell-based PD models) expertise to identify new genetic pathways that mediate protection against neurodegenerations during oxidative stress and aging. I expect that achieved goals of the proposal will be important discovery that should lead to novel therapeutic targeting for Parkinson’s disease, and other neurodegenerative proteinopathies. My long-term goal is to become an independent scientist and establish lab to find novel therapeutic targets and strategies for the diseases associated with oxidative stress, including PD. Gained research experience together with improving my teaching, mentoring and management skills during this fellowship will help me to achieve my goals and transition myself into independence.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-RI - RI – Reintegration panelCoordinatore
39100 Bolzano
Italia