Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice
- 주제(키워드) Parkinson's disease (PD) , Matrix metalloproteinase-8 (MMP-8) , Neuro-inflammation , Neuroprotection
- 주제(기타) Biochemistry & Molecular Biology; Pharmacology & Pharmacy
- 설명문(일반) [Kim, Taewoo; Jeon, Jeha; Park, Yeongwon; Kim, Jooeui; Noh, Haneul; Seo, Hyemyung] Hanyang Univ, Ctr Bionano Intelligence Educ & Res, Dept Mol & Life Sci, Ansan 15588, South Korea; [Park, Jin-Sun; Kim, Hee-Sun] Ewha Womans Univ, Sch Med, Dept Mol Med, Seoul 07804, South Korea; [Park, Jin-Sun; Kim, Hee-Sun] Ewha Womans Univ, Sch Med, Med Res Inst, Seoul 07804, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published
- 발행기관 KOREAN SOC APPLIED PHARMACOLOGY
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183725
- 본문언어 영어
- Published As http://dx.doi.org/10.4062/biomolther.2020.181
- PubMed https://pubmed.ncbi.nlm.nih.gov/34045367
초록/요약
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.
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