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Nonetheless, the mechanism of the abnormally increased MAO B activity in PD is still unclear. Previous research showed transcription factor specificity protein 1 (SP1) directly regulates MAO B activity by binding the SP1 binding sequence in MAO B promoter. In our study, we first observed that the SP1 protein level and SP1 binding activity in the MAO B promoter were increased in 1\u2010methyl\u20104\u2010phenylpyridinium (MPP<jats:sup>+<\/jats:sup>) neurotoxin\u2010induced SH\u2010SY5Y cells. Inhibition of SP1 by pretreatment with SP1 inhibitor mithramycin A (MMA) attenuated the abnormal increase in SP1 binding activity and the MAO B protein level to basal levels. Then, we investigated the neuroprotective effects of SP1 inhibition. In SH\u2010SY5Y cell models of PD, preincubation with MMA or knockdown by SP1\u2010specific small interfering RNA showed potent protection against MPP<jats:sup>+<\/jats:sup>\u2010induced apoptosis via SP1. In a male C57BL\/6 mouse model of PD, MAO B activity and MPP<jats:sup>+<\/jats:sup> concentrations in mouse brain following injection of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) were increased, whereas the elevated MAO B activity was decreased after pre\u2010injection of MMA. Moreover, MMA ameliorated MPTP\u2010induced loss of dopaminergic neurons in the substantia nigra pars compacta and mouse behavioral impairments. Altogether, our study suggests that SP1 is a principal factor regulating increases in MAO B activity, and SP1 inhibition produces neuroprotective effects in PD models through decreases in MAO B activity, which may be a new neuroprotective therapeutic strategy for PD treatment.<\/jats:p>","DOI":"10.1002\/jnr.24266","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T12:41:16Z","timestamp":1531485676000},"page":"1663-1676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Inhibition of transcription factor SP1 produces neuroprotective effects through decreasing MAO B activity in MPTP\/MPP<sup>+<\/sup> Parkinson's disease models"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6278-8564","authenticated-orcid":false,"given":"Lu","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic 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