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We have recently established that MMP\u20103 plays crucial roles in dopaminergic cell death and microglial activation.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> We tested the effects of 7\u2010hydroxy\u20106\u2010methoxy\u20102\u2010propionyl\u20101,2,3,4\u2010tetrahydroisoquinoline (PTIQ) on expression of MMP\u20103 and inflammatory molecules and dopaminergic cell death <jats:italic>in vitro<\/jats:italic> and in an animal model of Parkinson's disease, and Parkinson's disease\u2010related motor deficits. The pharmacokinetic profile of PTIQ was also evaluated.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> PTIQ effectively suppressed the production of MMP\u20103 induced in response to cellular stress in the dopaminergic CATH.a cell line and prevented the resulting cell death. In BV\u20102 microglial cells activated with lipopolysaccharide, PTIQ down\u2010regulated expression of MMP\u20103 along with IL\u20101\u03b2, TNF\u2010\u03b1 and cyclooxygenase\u20102 and blocked nuclear translocation of NF\u2010\u03baB. In the mouse model of Parkinson's disease ,induced by 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP), PTIQ attenuated the associated motor deficits, prevented neurodegeneration and suppressed microglial activation in the substantia nigra. Pharmacokinetic analysis showed it was relatively stable against liver microsomal enzymes, did not inhibit the cytochrome p450 isozymes or the hERG ion channel, exhibited no cytotoxicity on liver cells or lethality when administered at 1000\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> and entered the brain rather rapidly yielding a 28% brain:plasma ratio after i.p. injection.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> These results suggest PTIQ has potential as a candidate drug for disease\u2010modifying therapy for Parkinson's disease.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01692.x","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T01:20:27Z","timestamp":1317172827000},"page":"2213-2227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A novel compound PTIQ protects the nigral dopaminergic neurones in an animal model of Parkinson's disease 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