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Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice
- Source :
- Biomolecules & Therapeutics
- Publication Year :
- 2021
- Publisher :
- The Korean Society of Applied Pharmacology, 2021.
-
Abstract
- Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium- binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.
- Subjects :
- Pharmacology
medicine.medical_specialty
Parkinson's disease
Matrix metalloproteinase-8 (MMP-8)
Microglia
Tyrosine hydroxylase
business.industry
Substantia nigra
Striatum
Parkinson’s disease (PD)
medicine.disease
Biochemistry
Neuroprotection
LRRK2
Endocrinology
medicine.anatomical_structure
Neuro-inflammation
Internal medicine
Drug Discovery
Systemic administration
medicine
Molecular Medicine
Original Article
business
Subjects
Details
- ISSN :
- 20054483 and 19769148
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Biomolecules & Therapeutics
- Accession number :
- edsair.doi.dedup.....8f86ed05e9f29de7df1131785f60a4fc