Seminario | c-Myc-Driven Astrogliosis Impairs Neuron-Glia Communication in ALS

Mercoledì 7 maggio alle ore 16, in occasione degli incontri organizzati dal Dottorato in Scienze Biomediche (DSB) e dal Dottorato in Bioscienze (DiBIO), Prof. Emanuela Basso (Università degli Studi di Trento) presenta il seminario "c-Myc-Driven Astrogliosis Impairs Neuron-Glia Communication in ALS" presso l'Aula RG del Complesso Vallisneri, in via Ugo Bassi 58/B, Padova.

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.

HOSTS: Prof. Maria Pennuto, Prof. Michela Rigoni, Prof. Ornella Rossetto e Prof. Chiara Romualdi