PloS one, 2010-12, Vol.5 (12), p.e14192-e14192
2010
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease
- Ist Teil von
- PloS one, 2010-12, Vol.5 (12), p.e14192-e14192
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Neurodegenerative metabolic disorders such as mucopolysaccharidosis IIIB (MPSIIIB or Sanfilippo disease) accumulate undegraded substrates in the brain and are often unresponsive to enzyme replacement treatments due to the impermeability of the blood brain barrier to enzyme. MPSIIIB is characterised by behavioural difficulties, cognitive and later motor decline, with death in the second decade of life. Most of these neurodegenerative lysosomal storage diseases lack effective treatments. We recently described significant reductions of accumulated heparan sulphate substrate in liver of a mouse model of MPSIIIB using the tyrosine kinase inhibitor genistein. We report here that high doses of genistein aglycone, given continuously over a 9 month period to MPSIIIB mice, significantly reduce lysosomal storage, heparan sulphate substrate and neuroinflammation in the cerebral cortex and hippocampus, resulting in correction of the behavioural defects observed. Improvements in synaptic vesicle protein expression and secondary storage in the cerebral cortex were also observed. Genistein may prove useful as a substrate reduction agent to delay clinical onset of MPSIIIB and, due to its multimodal action, may provide a treatment adjunct for several other neurodegenerative metabolic diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0014192Titel-ID: cdi_plos_journals_1318939925
- Format
- –
- Schlagworte
- Aglycones, Analysis, Angiogenesis inhibitors, Animals, Blood-Brain Barrier, Bone marrow, Brain, Brain - metabolism, Brain research, Breast cancer, Cancer therapies, Cerebral cortex, Cognitive ability, Disease, Disease Models, Animal, Enzyme inhibitors, Enzymes, Gene Expression Regulation, Genistein, Genistein - pharmacology, Glycine max, Heparan sulfate, Heparitin Sulfate - chemistry, Heterozygote, Hospitals, Immunohistochemistry - methods, Inflammation, Isoflavones, Liver, Liver - metabolism, Lysosomal storage diseases, Lysosomes - metabolism, Medical research, Medical treatment, Metabolic disorders, Metabolism, Mice, Mice, Inbred C57BL, Molecular biology, Mucopolysaccharidosis, Mucopolysaccharidosis III - metabolism, Neurodegeneration, Neurodegenerative Diseases - metabolism, Neurological Disorders/Neurogenetics, Neurons - metabolism, Neuroscience/Neurobiology of Disease and Regeneration, Permeability, Pharmacology/Drug Development, Protein Kinase Inhibitors - pharmacology, Protein-tyrosine kinase, Proteins, Rodents, Science, Stem cells, Storage, Substrates, Sulfates, Transplants & implants, Tyrosine, Womens health