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)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

CLAUDIA VERDERIO
Phone number: 0250317098
Email: 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".

Goals

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.

Start date of activity

18/03/2019

Keywords

microglia, progranulin C, C9orf72

Last update: 17/06/2025