title: Autophagy in astrocytes: a novel culprit in lysosomal storage disorders.
abstract: Neurodegeneration is a prominent feature of lysosomal storage disorders (LSDs). Emerging data identify autophagy dysfunction in neurons as a major component of the phenotype. However, the autophagy pathway in the CNS has been studied predominantly in neurons, whereas in other cell types it has been largely unexplored. We studied the lysosome-autophagic pathway in astrocytes from a murine model of multiple sulfatase deficiency (MSD), a severe form of LSD. Similar to what was observed in neurons, we found that lysosomal storage in astrocytes impairs autophagosome maturation and this, in turn, has an impact upon the survival of cortical neurons and accounts for some of the neurological features found in MSD. Thus, our data indicate that lysosomal/autophagic dysfunction in astrocytes is an important component of neurodegeneration in LSDs.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Malta
authors.forename: John D
authors.initials: JD
authors.lastname: Fryer
authors.forename: Carmine
authors.initials: C
authors.lastname: Settembre
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology*; D001343:Autophagy; D007249:Inflammation / Q000473:pathology; D016464:Lysosomal Storage Diseases / Q000201:enzymology / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D013429:Sulfatases / Q000172:deficiency / Q000378:metabolism
chemical_list: D013429:Sulfatases