Melania Scarcella, Gianluca Scerra, Mariangela Ciampa, Marianna Caterino, Michele Costanzo, Laura Rinaldi, Antonio Feliciello, Serenella Anzilotti, Chiara Fiorentino, Maurizio Renna, Margherita Ruoppolo, Luigi Michele Pavone, Massimo D'Agostino, Valeria De Pasquale
Mucopolysaccharidoses (MPSs) are lysosomal disorders with neurological involvement for which no cure exists. Here, we show that recombinant NK1 fragment of hepatocyte growth factor rescues substrate accumulation and lysosomal defects in MPS I, IIIA and IIIB patient fibroblasts. We investigated PI3K/Akt pathway, which is of crucial importance for neuronal function and survival, and demonstrate that PI3K inhibition abolishes NK1 therapeutic effects. We identified that autophagy inhibition, by Beclin1 silencing, reduces MPS IIIB phenotype and that NK1 downregulates autophagic-lysosome (ALP) gene expression, suggesting a possible contribution of autophagosome biogenesis in MPS...
March 15, 2024: IScience