Dataset Information

Astrogliosis and miscommunication in ALS

ABSTRACT: Chronic activation of glial cells leads to the dysfunction and degeneration of motor and cortical neurons in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with an unknown mechanism. To shed light on the molecular pathogenetic processes underlying the exordium and contribution of gliosis to disease onset and progression, we used cells, mice, and patient-derived cells modeling TDP-43, SOD1, and C9orf72-linked and sporadic ALS. We identify an initial phase of the disease marked by increased astrocyte proliferation, followed by a typical activation stage with elevated expression of pro-inflammatory genes. Using mouse genetics, we show that expression of mutant TDP-43 in astrocytes is necessary to cause gliosis and behavioral abnormalities. Mechanistically, we show that c-Myc gain-of-function drives astrocyte proliferation by promoting the release of EVs that nonetheless fail to provide trophic support to surrounding neurons. Our research reveals a novel functional role for c-Myc in astrocytes in the miscommunication from glia to neurons in ALS.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cerebral Cortical Neuronï¿½

SUBMITTER: Romina Belli

LAB HEAD: Manuela Basso

PROVIDER: PXD064120 | Pride | 2026-06-29

REPOSITORIES: Pride

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MYC-driven gliosis impairs neuron-glia communication in amyotrophic lateral sclerosis.

Fioretti Paolo V PV Barbieri Anna A Migazzi Alice A Bressan Davide D Grassano Maurizio M Donini Luisa L Roccuzzo Michela M Torrieri Maria Claudia MC Conci Francesca F Ferracci Elisa E Invernizzi Sabrina S Bowden Katie M KM Bacchetti Francesca F Cappelli Sara S Peroni Daniele D Belli Romina R Pancher Michael M Mugoni Vera V Scarduelli Giorgina G Gianesello Matteo M Pasetto Laura L Canarutto Giulia G Carra Serena S Soldano Alessia A Bisio Alessandra A Robbiati Sergio S Valentini Chiara C Nardella Caterina C Piazza Silvano S D'Agostino Vito G VG Quattrone Alessandro A Sleiman Sama S Whitfield Jonathan R JR Soucek Laura L Vignoli Beatrice B Viero Gabriella G Tiberi Luca L Zippo Alessio A Demichelis Francesca F Bonetto Valentina V Milanese Marco M Buratti Emanuele E Verde Federico F Ticozzi Nicola N Calvo Andrea A Ratti Antonia A Shaw Pamela J PJ Terenzio Marco M Chiacchiera Fulvio F Pennuto Maria M Basso Manuela M

Brain : a journal of neurology 20260501 5

Chronic activation of glial cells leads to the dysfunction and degeneration of motor and cortical neurons in amyotrophic lateral sclerosis and frontotemporal dementia with an unknown mechanism. To shed light on the molecular pathogenetic processes underlying the exordium and contribution of gliosis to disease onset and progression, we used cells, mice and patient-derived cells modelling TDP-43, SOD1 and C9ORF72-linked and sporadic ALS. Our data reveal a sequential disease progression, starting w ...[more]

PMID: 41004427

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	Lysate.mzid	Mzid
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	TDP-43-Q331K-Cherry2.raw	Raw
	TDP-43-Q331K-Cherry3.raw	Raw