Region-Specific Alterations of Matrix Metalloproteinase Activity in Multiple System Atrophy

Fares Bassil, Arnaud Monvoisin, Marie-Helene Canron, Anne Vital, Wassilios G. Meissner, François Tison, Pierre-Olivier Fernagut
Mov Disord.. 2015-08-11; 30(13): 1802-1812
DOI: 10.1002/mds.26329

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1. Mov Disord. 2015 Nov;30(13):1802-12. doi: 10.1002/mds.26329. Epub 2015 Aug 11.

Region-Specific Alterations of Matrix Metalloproteinase Activity in Multiple
System Atrophy.

Bassil F(1)(2), Monvoisin A(3), Canron MH(1)(2), Vital A(1)(2)(4), Meissner
WG(1)(2)(5)(6), Tison F(1)(2)(5)(6), Fernagut PO(1)(2).

Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(2)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
(3)Université de Poitiers, Signalisation & Transports Ioniques Membranaires,
ERL7368 CNRS, Poitiers, France.
(4)Service d’Anatomie Pathologique, CHU de Bordeaux, Bordeaux, France.
(5)Service de Neurologie, CHU de Bordeaux, Bordeaux, France.
(6)Centre de référence atrophie multisystématisée, CHU de Bordeaux, Bordeaux,

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

© 2015 International Parkinson and Movement Disorder Society.

DOI: 10.1002/mds.26329
PMID: 26260627 [Indexed for MEDLINE]

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