Veronica Ferrari, Riccardo Cristofani, Maria E Cicardi, Barbara Tedesco, Valeria Crippa, Marta Chierichetti, Elena Casarotto, Marta Cozzi, Francesco Mina, Mariarita Galbiati, Margherita Piccolella, Serena Carra, Thomas Vaccari, Angele Nalbandian, Virginia Kimonis, Tyler R Fortuna, Udai B Pandey, Maria C Gagliani, Katia Cortese, Paola Rusmini, Angelo Poletti
AIM: Mutations in the valosin-containing protein (VCP) gene cause various lethal proteinopathies that mainly include inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and amyotrophic lateral sclerosis (ALS). Different pathological mechanisms have been proposed. Here, we define the impact of VCP mutants on lysosomes and how cellular homeostasis is restored by inducing autophagy in the presence of lysosomal damage. METHODS: By electron microscopy, we studied lysosomal morphology in VCP animal and motoneuronal models...
August 2022: Neuropathology and Applied Neurobiology