FINALIZZATA MIN SAL - Dissecting molecular mechanisms triggered by progressive loss of progranulin and C9ORF72 in frontotemporal dementia: novel therapeutic targets? - Resp. C. Verderio (DSB.AD004.233)
Area tematica
Area progettuale
Neuroscienze (DSB.AD004)Struttura responsabile del progetto di ricerca
Responsabile di progetto
CLAUDIA VERDERIO
Telefono: 0250317098
E-mail: claudia.verderio@in.cnr.it
Abstract
GRN and C9orf72 expression is reduced in a substantial number of frontotemporal dementia (FTD) patients and a correlation between progressive loss of GRN/C9orf72 and clinical phenotype has been reported. Cutting edge molecular research suggests that Immune dysregulation, neurotoxic microglia activation, lysosomal/exosomal dysfunctions are pathological events derived by loss of functional proteins in GRN/C9orf72-associated FTD. We hypothesize a connection between "progressive loss of expression-specific molecular mechanism-clinical phenotype".
Obiettivi
Here, we aim to dissect molecular mechanisms associated with a progressive GRN/C9orf72 loss by i) generating ad hoc human cell disease models; ii) testing whether EVs secreted from GRN/C9orf72 silenced microglia deliver excessive complements factors to the synapses, thus causing aberrant synaptic pruning; iii) Studying whether lysosomal and immune proteins, especially those associated to EVs, represent biomarkers for familiar and sporadic FTD.
Data inizio attività
18/03/2019
Parole chiave
microglia, progranulin C, C9orf72
Ultimo aggiornamento: 20/05/2024