Mucopolysaccharidosis IIIB: oxidative damage and cytotoxic cell involvement in the neuronal pathogenesis

Brain Res. 2009 Jul 7;1279:99-108. doi: 10.1016/j.brainres.2009.03.071. Epub 2009 May 3.


Sanfilippo B syndrome (Mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease due to mutations in the gene encoding alpha-N-acetylglucosaminidase and is characterized by a severe neurological disorder. Although several studies have been reported for the murine model of the disease, the molecular basis and the sequence of events leading to neurodegeneration remain to be clarified. We previously suggested the possible involvement of the reactive oxygen species in the disease pathogenesis. In the present paper we extended the analysis of oxidative stress by evaluating the production of superoxide ions throughout the CNS and by evaluating the effect of the stress on the cellular macromolecules. These approaches applied to one-month-old, three-month-old and six-month-old mice revealed that oxidative stress is present in the affected cerebrum and cerebellum tissues from one month from birth, and that it results primarily in protein oxidation, both in the cerebrum and cerebellum, with lipid peroxidation, and especially DNA oxidation, appearing milder and restricted essentially to the cerebellum. We also identified additional genes possibly associated with the neuropathology of MPS IIIB disease. Real time RT-PCR analysis revealed an altered expression of the Sod1, Ret, Bmp4, Tgfb, Gzmb and Prf1 genes. Since Gzmb and Prf1 are proteins secreted by NK/cytotoxic T-cells, these data suggest the involvement of cytotoxic cells in the neuronal pathogenesis. Extending our previous study, findings reported in the present paper show that oxidative stress and all the analyzed stress-related pathological changes occur very early in the disease course, most likely before one month of age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism
  • Brain / growth & development*
  • Brain / physiopathology*
  • DNA / metabolism
  • Granzymes / genetics
  • Granzymes / metabolism
  • Lipid Peroxidation
  • Mice
  • Mucopolysaccharidosis III / genetics
  • Mucopolysaccharidosis III / physiopathology*
  • NADP / metabolism
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Perforin
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / metabolism
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins c-ret / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Superoxides / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Pore Forming Cytotoxic Proteins
  • Transforming Growth Factor beta
  • perforin 1, mouse
  • Superoxides
  • Perforin
  • NADP
  • DNA
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Proto-Oncogene Proteins c-ret
  • Ret protein, mouse
  • Granzymes
  • Gzmb protein, mouse