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We have shown that interventions that simultaneously increase the neuroprotective<jats:styled-content style=\"fixed-case\">GM1<\/jats:styled-content>ganglioside and decrease the pro\u2010apoptotic<jats:styled-content style=\"fixed-case\">GD3<\/jats:styled-content>ganglioside\u00a0\u2013\u00a0such as inhibition of<jats:styled-content style=\"fixed-case\">GD3<\/jats:styled-content>synthase (<jats:styled-content style=\"fixed-case\">GD3S<\/jats:styled-content>) or administration of sialidase\u00a0\u2013\u00a0are neuroprotective<jats:italic>in vitro<\/jats:italic>and in a number of preclinical models. In this study, we investigated the effects of<jats:styled-content style=\"fixed-case\">GD3S<\/jats:styled-content>deletion on parkinsonism induced by 1\u2010methyl\u20104phenyl\u20101,2,3,6\u2010tetrahydropyridine (<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>).<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>was administered to<jats:styled-content style=\"fixed-case\">GD3S<\/jats:styled-content>\u2212\/\u2212 mice or controls using a subchronic regimen consisting of three series of low\u2010dose injections (11\u2009mg\/kg\/day\u2009\u00d7\u20095\u2009days each, 3\u2009weeks apart), and motor function was assessed after each. The typical battery of tests used to assess parkinsonism failed to detect deficits in<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>\u2010treated mice. More sensitive measures\u00a0\u2013\u00a0such as the force\u2010plate actimeter and treadmill gait parameters\u00a0\u2013\u00a0detected subtle effects of<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>, some of which were absent in mice lacking<jats:styled-content style=\"fixed-case\">GD3S<\/jats:styled-content>. In wild\u2010type mice,<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>destroyed 53% of the tyrosine\u2010hydroxylase (<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>)\u2010positive neurons in the substantia nigra pars compacta (<jats:styled-content style=\"fixed-case\">SNc<\/jats:styled-content>) and reduced striatal dopamine 60.7%. In contrast, lesion size was only 22.5% in<jats:styled-content style=\"fixed-case\">GD3S<\/jats:styled-content>\u2212\/\u2212 mice and striatal dopamine was reduced by 37.2%. Stereological counts of Nissl\u2010positive<jats:styled-content style=\"fixed-case\">SNc<\/jats:styled-content>neurons that did not express<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>suggest that neuroprotection was complete but<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>expression was suppressed in some cells. These results show that inhibition of<jats:styled-content style=\"fixed-case\">GD3S<\/jats:styled-content>has neuroprotective properties in the<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>model and may warrant further investigation as a therapeutic target.<\/jats:p>","DOI":"10.1111\/gbb.12377","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T06:22:43Z","timestamp":1488176563000},"page":"522-536","source":"Crossref","is-referenced-by-count":22,"title":["Targeted deletion of<scp>GD3<\/scp>synthase protects against<scp>MPTP<\/scp>\u2010induced neurodegeneration"],"prefix":"10.1111","volume":"16","author":[{"given":"Y.","family":"Akkhawattanangkul","sequence":"first","affiliation":[{"name":"Department of Comparative Medicine University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Maiti","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Aryal","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioral Sciences Duke University Medical Center Durham NC USA"},{"name":"Department of Cell Biology Duke University Medical Center Durham NC USA"},{"name":"Department of Neurobiology Duke University Medical Center Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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