TY - JOUR
T1 - Loss of exosomes in progranulin-associated frontotemporal dementia
AU - Benussi, Luisa
AU - Ciani, Miriam
AU - Tonoli, Elisa
AU - Morbin, Michela
AU - Palamara, Luisa
AU - Albani, Diego
AU - Fusco, Federica
AU - Forloni, Gianluigi
AU - Glionna, M.
AU - Baco, Monika
AU - Paterlini, Anna
AU - Fostinelli, Silvia
AU - Santini, Benedetta
AU - Galbiati, Elisabetta
AU - Gagni, Paola
AU - Cretich, Marina
AU - Binetti, Giuliano
AU - Tagliavini, Fabrizio
AU - Prosperi, Davide
AU - Chiari, Marcella
AU - Ghidoni, Roberta
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Many cells of the nervous system have been shown to release exosomes, a subclass of secreted vesicles of endosomal origin capable of transferring biomolecules among cells: this transfer modality represents a novel physiological form of intercellular communication between neural cells. Herein, we demonstrated that progranulin (PGRN), a protein targeted to the classical secretory pathway, is also secreted in association with exosomes by human primary fibroblasts. Moreover, we demonstrated that null mutations in the progranulin gene (GRN), a major cause of frontotemporal dementia, strongly reduce the number of released exosomes and alter their composition. In vitro GRN silencing in SHSY-5Y cells confirmed a role of PGRN in the control of exosome release. It is believed that depletion of PGRN in the brain might cause neurodegeneration in GRN-associated frontotemporal dementia. We demonstrated that, along with shortage of the circulating PGRN, GRN null mutations alter intercellular communication. Thus, a better understanding of the role played by exosomes in GRN-associated neurodegeneration is crucial for the development of novel therapies for these diseases.
AB - Many cells of the nervous system have been shown to release exosomes, a subclass of secreted vesicles of endosomal origin capable of transferring biomolecules among cells: this transfer modality represents a novel physiological form of intercellular communication between neural cells. Herein, we demonstrated that progranulin (PGRN), a protein targeted to the classical secretory pathway, is also secreted in association with exosomes by human primary fibroblasts. Moreover, we demonstrated that null mutations in the progranulin gene (GRN), a major cause of frontotemporal dementia, strongly reduce the number of released exosomes and alter their composition. In vitro GRN silencing in SHSY-5Y cells confirmed a role of PGRN in the control of exosome release. It is believed that depletion of PGRN in the brain might cause neurodegeneration in GRN-associated frontotemporal dementia. We demonstrated that, along with shortage of the circulating PGRN, GRN null mutations alter intercellular communication. Thus, a better understanding of the role played by exosomes in GRN-associated neurodegeneration is crucial for the development of novel therapies for these diseases.
KW - Exosomes
KW - Extracellular vesicles
KW - GRN
KW - Human primary fibroblasts
KW - Null mutations
KW - Progranulin
UR - http://www.scopus.com/inward/record.url?scp=84960406260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84960406260&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.01.001
DO - 10.1016/j.neurobiolaging.2016.01.001
M3 - Article
AN - SCOPUS:84960406260
VL - 40
SP - 41
EP - 49
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -