Matrix metalloproteinase-8 inhibitor ameliorates inflammatory responses and behavioral deficits in lrrk2 g2019s parkinson’s disease model mice

Taewoo Kim, Jeha Jeon, Jin Sun Park, Yeongwon Park, Jooeui Kim, Haneul Noh, Hee Sun Kim, Hyemyung Seo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 cal-cium-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.

Original languageEnglish
Pages (from-to)483-491
Number of pages9
JournalBiomolecules and Therapeutics
Volume29
Issue number5
DOIs
StatePublished - Sep 2021

Keywords

  • Matrix metalloproteinase-8 (MMP-8)
  • Neuro-inflammation
  • Neuroprotection
  • Parkinson’s disease (PD)

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