{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:49:36Z","timestamp":1791946176712,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":273,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> The peroxisome proliferator\u2010activated receptor\u2010\u03b3 (PPAR\u03b3) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) mouse model of Parkinson's disease, an effect attributed to its anti\u2010inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse model, not via an anti\u2010inflammatory action, but through inhibition of MAO\u2010B, the enzyme required to biotransform MPTP to its active neurotoxic metabolite 1\u2010methyl\u20104\u2010phenylpyridinium (MPP+).<\/jats:p><jats:p><jats:bold>Experimental approach:<\/jats:bold> Mice were treated with pioglitazone (20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> b.i.d. (twice a day), p.o., for 7 days), prior and post or post\u2010MPTP (30\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> s.c.) treatment. Mice were then assessed for motor impairments on a beam\u2010walking apparatus and for reductions in TH immunoreactivity in the substantia nigra and depletions in striatal dopamine. The effects of pioglitazone on striatal MPP+ levels and MAO\u2010B activity were also assessed.<\/jats:p><jats:p><jats:bold>Key results:<\/jats:bold> Mice treated with MPTP showed deficits in motor performance, marked depletions in striatal dopamine levels and a concomitant reduction in TH immunoreactivity in the substantia nigra. Pretreatment with pioglitazone completely prevented these effects of MPTP. However, pretreatment with pioglitazone also significantly inhibited the MPTP\u2010induced production of striatal MPP+ and the activity of MAO\u2010B in the striatum.<\/jats:p><jats:p><jats:bold>Conclusions and implications:<\/jats:bold> The neuroprotection observed with pioglitazone pretreatment in the MPTP mouse model was due to the blockade of the conversion of MPTP to its active toxic metabolite MPP+, via inhibition of MAO\u2010B.<\/jats:p>","DOI":"10.1038\/bjp.2008.78","type":"journal-article","created":{"date-parts":[[2008,3,10]],"date-time":"2008-03-10T12:38:21Z","timestamp":1205152701000},"page":"226-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["The PPAR\u03b3 agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B"],"prefix":"10.1111","volume":"154","author":[{"given":"L 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