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.

Benussi, L., Ciani, M., Tonoli, E., Morbin, M., Palamara, L., Albani, D., et al. (2016). Loss of exosomes in progranulin-associated frontotemporal dementia. NEUROBIOLOGY OF AGING, 40, 41-49 [10.1016/j.neurobiolaging.2016.01.001].

Loss of exosomes in progranulin-associated frontotemporal dementia

SANTINI, BENEDETTA;GALBIATI, ELISABETTA;PROSPERI, DAVIDE;
2016

Abstract

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.
Articolo in rivista - Articolo scientifico
Exosomes; Extracellular vesicles; GRN; Human primary fibroblasts; Null mutations; Progranulin;
Exosomes; Extracellular vesicles; GRN; Human primary fibroblasts; Null mutations; Progranulin; Neuroscience (all); Medicine (all); Aging; Developmental Biology; Geriatrics and Gerontology; Neurology (clinical)
English
41
49
9
Benussi, L., Ciani, M., Tonoli, E., Morbin, M., Palamara, L., Albani, D., et al. (2016). Loss of exosomes in progranulin-associated frontotemporal dementia. NEUROBIOLOGY OF AGING, 40, 41-49 [10.1016/j.neurobiolaging.2016.01.001].
Benussi, L; Ciani, M; Tonoli, E; Morbin, M; Palamara, L; Albani, D; Fusco, F; Forloni, G; Glionna, M; Baco, M; Paterlini, A; Fostinelli, S; Santini, B; Galbiati, E; Gagni, P; Cretich, M; Binetti, G; Tagliavini, F; Prosperi, D; Chiari, M; Ghidoni, R
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/138706
Citazioni
  • Scopus 39
  • ???jsp.display-item.citation.isi??? 36
Social impact