Region-Specific Alterations of Matrix Metalloproteinase Activity in Multiple System Atrophy
| Autor: | Anne Vital, François Tison, Arnaud Monvoisin, Fares Bassil, Marie-Hélène Canron, Pierre-Olivier Fernagut, Wassilios G. Meissner |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Microglia Glial fibrillary acidic protein biology Putamen Neurodegeneration Matrix metalloproteinase medicine.disease nervous system diseases Myelin medicine.anatomical_structure nervous system Neurology mental disorders medicine biology.protein Neuroglia Neurology (clinical) Neuroinflammation |
| Zdroj: | Movement Disorders. 30:1802-1812 |
| ISSN: | 0885-3185 |
| Popis: | Background MSA is a sporadic progressive neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction. The pathological hallmark of MSA is the accumulation of alpha-synuclein aggregates in the cytoplasm of oligodendrocytes along with neuronal loss and neuroinflammation, as well as blood–brain barrier dysfunction and myelin deterioration. Matrix metalloproteinases are zinc-dependent endopeptidases involved in the remodeling of the extracellular matrix, demyelination, and blood–brain barrier permeability. Several lines of evidence indicate a role for these enzymes in various pathological processes, including stroke, multiple sclerosis, Parkinson's, and Alzheimer's disease. Methods This study aimed to assess potential alterations of matrix metalloproteinase-1, -2, -3, and -9 expression or activity in MSA postmortem brain tissue. Results Gelatin zymography revealed increased matrix metalloproteinase-2 activity in the putamen, but not in the frontal cortex, of MSA patients relative to controls. Immunohistochemistry revealed increased number of glial cells positive for matrix metalloproteinase-1, -2, and -3 in the putamen and frontal cortex of MSA patients. Double immunofluorescence revealed that matrix metalloproteinase-2 and -3 were expressed in astrocytes and microglia. Only matrix metalloproteinase-2 colocalized with alpha-synuclein in oligodendroglial cytoplasmic inclusions. Conclusion These results demonstrate widespread alterations of matrix metalloproteinase expression in MSA and a pattern of increased matrix metalloproteinase-2 expression and activity affecting preferentially a brain region severely affected (putamen) over a relatively spared region (frontal cortex). Elevated matrix metalloproteinase expression may thus contribute to the disease process in MSA by promoting blood–brain barrier dysfunction and/or myelin degradation. © 2015 International Parkinson and Movement Disorder Society |
| Databáze: | OpenAIRE |
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