Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson's Disease
File(s)
Accepted version
Author(s)
Hurley, MJ
Durrenberger, PF
Gentleman, SM
Walls, AF
Dexter, DT
Type
Journal Article
Abstract
Neuroinflammation is thought to contribute to cell
death in neurodegenerative disorders, but the factors involved
in the inflammatory process are not completely understood.
Proteinase-activated receptor-2 (PAR2) expression in brain is
increased in Alzheimer’s disease and multiple sclerosis, but
the status of PAR2 in Parkinson’s disease is unknown. This
study examined expression of PAR2 and endogenous proteinase
activators (trypsin-2, mast cell tryptase) and proteinase
inhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistant
to neurodegeneration in Parkinson’s disease at different
Braak α-synuclein stages of the disease in post-mortem brain.
In normal aged brain, expression of PAR-2, trypsin-2, and
serpin-A5 and serpin-A13 was found in neurons and microglia,
and alterations in the amount of immunoreactivity for these
proteins were found in some brain regions. Namely, there
was a decrease in neurons positive for serpin-A5 in the dorsal
motor nucleus, and serpin-A13 expression was reduced in the
locus coeruleus and primary motor cortex, while expression of
PAR2, trypsin-2 and both serpins was reduced in neurons
within the substantia nigra. There was an increased number
of microglia that expressed serpin-A5 in the dorsal motor nucleus
of vagus and elevated numbers of microglia that
expressed serpin-A13 in the substantia nigra of late
Parkinson’s disease cases. The number of microglia that
expressed trypsin-2 increased in primary motor cortex of incidental
Lewy body disease cases. Analysis of Parkinson’s
disease cases alone indicated that serpin-A5 and serpin-A13,
and trypsin-2 expression in midbrain and cerebral cortex was
different in cases with a high incidence of L-DOPA-induced
dyskinesia and psychosis compared to those with low levels of
these treatment-induced side effects. This study showed that
there was altered expression in brain of PAR2 and some proteins
that can control its function in Parkinson’s disease. Given
the role of PAR2 in neuroinflammation, drugs that mitigate
these changes may be neuroprotective when administered to
patients with Parkinson’s disease
death in neurodegenerative disorders, but the factors involved
in the inflammatory process are not completely understood.
Proteinase-activated receptor-2 (PAR2) expression in brain is
increased in Alzheimer’s disease and multiple sclerosis, but
the status of PAR2 in Parkinson’s disease is unknown. This
study examined expression of PAR2 and endogenous proteinase
activators (trypsin-2, mast cell tryptase) and proteinase
inhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistant
to neurodegeneration in Parkinson’s disease at different
Braak α-synuclein stages of the disease in post-mortem brain.
In normal aged brain, expression of PAR-2, trypsin-2, and
serpin-A5 and serpin-A13 was found in neurons and microglia,
and alterations in the amount of immunoreactivity for these
proteins were found in some brain regions. Namely, there
was a decrease in neurons positive for serpin-A5 in the dorsal
motor nucleus, and serpin-A13 expression was reduced in the
locus coeruleus and primary motor cortex, while expression of
PAR2, trypsin-2 and both serpins was reduced in neurons
within the substantia nigra. There was an increased number
of microglia that expressed serpin-A5 in the dorsal motor nucleus
of vagus and elevated numbers of microglia that
expressed serpin-A13 in the substantia nigra of late
Parkinson’s disease cases. The number of microglia that
expressed trypsin-2 increased in primary motor cortex of incidental
Lewy body disease cases. Analysis of Parkinson’s
disease cases alone indicated that serpin-A5 and serpin-A13,
and trypsin-2 expression in midbrain and cerebral cortex was
different in cases with a high incidence of L-DOPA-induced
dyskinesia and psychosis compared to those with low levels of
these treatment-induced side effects. This study showed that
there was altered expression in brain of PAR2 and some proteins
that can control its function in Parkinson’s disease. Given
the role of PAR2 in neuroinflammation, drugs that mitigate
these changes may be neuroprotective when administered to
patients with Parkinson’s disease
Date Issued
2015-05-17
Date Acceptance
2015-05-05
Citation
Journal of Molecular Neuroscience, 2015, 57 (1), pp.48-62
ISSN
1559-1166
Publisher
Springer
Start Page
48
End Page
62
Journal / Book Title
Journal of Molecular Neuroscience
Volume
57
Issue
1
Copyright Statement
The final publication is available at Springer via https://dx.doi.org/10.1007/s12031-015-0576-8
Sponsor
Michael J Fox Foundation
Grant Number
RRIA 2013
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Neurosciences & Neurology
Dyskinesia
L-DOPA
Neuroinflammation
Parkinson's disease
Proteinase-activated receptor-2
Serpin (serine proteinase inhibitor clade A)
TISSUE-PLASMINOGEN ACTIVATOR
LONG-TERM POTENTIATION
MAST-CELL TRYPTASE
ALZHEIMERS-DISEASE
MULTIPLE-SCLEROSIS
INDUCED DYSKINESIA
PROTEASE
INFLAMMATION
NEUROINFLAMMATION
MICROGLIA
Publication Status
Published