title: Pathogenesis, Emerging therapeutic targets and Treatment in Sialidosis.
abstract: BACKGROUND
  Sialidosis is a neurosomatic, lysosomal storage disease (LSD) caused by mutations in theNEU1gene, encoding the lysosomal sialidase NEU1. Deficient enzyme activity results in impaired processing/degradation of sialo-glycoproteins, and accumulation of oversialylated metabolites. Sialidosis is considered an orphan disorder for which no therapy is currently available.
  
  
  METHODS
  The review describes the clinical forms of sialidosis and theNEU1mutations so far identified; NEU1 requirement to complex with the protective protein/cathepsin A for stability and activation; and the pathogenic effects of NEU1 deficiency. Studies of the molecular mechanisms of pathogenesis in animal models uncovered basic cellular pathways downstream of NEU1 and its substrates, which may be implicated in more common adult (neurodegenerative) diseases. The development of a Phase I/II clinical trial for patients with galactosialidosis may prove suitable for sialidosis patients with the attenuated form of the disease.
  
  
  CONCLUSIONS
  Recently, there has been a renewed interest in the development of therapies for orphan LSDs, like sialidosis. Given the small number of potentially eligible patients, the way to treat sialidosis would be through the coordinated effort of clinical centers, which provide diagnosis and care for these patients, and the basic research labs that work towards understanding the disease pathogenesis.
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: d'Azzo
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Eda
authors.initials: E
authors.lastname: Machado
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Ida
authors.initials: I
authors.lastname: Annunziata
keywords: NEU1; chaperone-mediated therapy; lysosomal exocytosis; lysosomal storage disease; mechanisms of pathogenesis; sialidosis