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Mucopolysaccharidosis IIIB: oxidative damage and cytotoxic cell involvement in the neuronal pathogenesis
- Source :
- Brain research. 1279
- Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Pore Forming Cytotoxic Proteins
Aging
pathogenesi
cell-mediated cytotoxicity
Mucopolysaccharidosis
SOD1
Bone Morphogenetic Protein 4
Biology
Protein oxidation
medicine.disease_cause
Granzymes
GZMB
Pathogenesis
Mice
Mucopolysaccharidosis III
Superoxide Dismutase-1
Superoxides
Transforming Growth Factor beta
medicine
Lysosomal storage disease
Animals
Mucopolysaccharidosis IIIB
Molecular Biology
oxidative stre
Perforin
Superoxide Dismutase
General Neuroscience
Neurodegeneration
Proto-Oncogene Proteins c-ret
neurodegeneration
Brain
DNA
medicine.disease
Oxidative Stress
Immunology
Nerve Degeneration
Neurology (clinical)
Lipid Peroxidation
Oxidation-Reduction
Oxidative stress
NADP
Developmental Biology
Subjects
Details
- ISSN :
- 18726240
- Volume :
- 1279
- Database :
- OpenAIRE
- Journal :
- Brain research
- Accession number :
- edsair.doi.dedup.....969d2ca2d112a0655616cdf1fb2909e5