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The cause and mechanisms underlying the demise of nigrostriatal <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic neurons are ill\u2010defined, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. Current evidence points to reactive glia as a pivotal factor in <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> pathophysiology, playing both protective and destructive roles. Here, the contribution of reactive astrocytes and their ability to modulate <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic neurodegeneration, neuroprotection and neurorepair in the 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>) rodent model of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> will be discussed in the light of novel emerging evidence implicating wingless\u2010type mouse mammary tumor virus integration site (Wnt)\/\u03b2\u2010catenin signaling as a strong candidate in <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>\u2010induced nigrostriatal <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic plasticity. In this work, we highlight an intrinsic <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>nt1\/frizzled\u20101\/\u03b2\u2010catenin tone that critically contributes to the survival and protection of adult midbrain <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic neurons, with potential implications for drug design or drug action in <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. The dynamic interplay between astrocyte\u2010derived factors and neurogenic signals in <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>\u2010induced nigrostriatal <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic neurotoxicity and repair will be summarized, together with recent findings showing a critical role of glia\u2013neural stem\/progenitor cell (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) interactions aimed at overcoming neurodegeneration and inducing neurorestoration. Understanding the intrinsic plasticity of nigrostriatal <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic neurons and deciphering the signals facilitating the crosstalk between astrocytes, microglia, <jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>ergic neurons and <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>s may have major implications for the role of stem cell technology in <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, and for identifying potential therapeutic targets to induce endogenous neurorepair.<\/jats:p>","DOI":"10.1111\/ejn.12166","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T03:33:13Z","timestamp":1362540793000},"page":"1550-1563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Uncovering novel actors in astrocyte\u2013neuron crosstalk in <scp>P<\/scp>arkinson's disease: the <scp>W<\/scp>nt\/\u03b2\u2010catenin signaling cascade as the common final pathway for neuroprotection and self\u2010repair"],"prefix":"10.1111","volume":"37","author":[{"given":"Bianca","family":"Marchetti","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Biomedicine Pharmacology Section Medical School University of Catania Catania Italy"},{"name":"Section of Neuropharmacology OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS) Via Conte Ruggero 73 94018 Troina (EN) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"L'Episcopo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Biomedicine Pharmacology Section Medical School University of Catania Catania Italy"},{"name":"Section of Neuropharmacology OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS) Via Conte Ruggero 73 94018 Troina (EN) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concetta","family":"Morale","sequence":"additional","affiliation":[{"name":"Section of Neuropharmacology OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS) Via Conte Ruggero 73 94018 Troina (EN) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cataldo","family":"Tirolo","sequence":"additional","affiliation":[{"name":"Section of Neuropharmacology OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS) Via Conte Ruggero 73 94018 Troina (EN) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuccio","family":"Testa","sequence":"additional","affiliation":[{"name":"Section of Neuropharmacology OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS) Via Conte Ruggero 73 94018 Troina (EN) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvo","family":"Caniglia","sequence":"additional","affiliation":[{"name":"Section of Neuropharmacology OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS) Via Conte Ruggero 73 94018 Troina (EN) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Serapide","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences Medical School University of Catania Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pluchino","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences Cambridge Centre for Brain Repair and Stem Cell Initiative University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.13.3797"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1868"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0177"},{"key":"e_1_2_12_5_1","first-page":"2287","article-title":"A unified hypothesis on the lineage of neural stem cells","volume":"2","author":"Alvarez\u2010Builla A.","year":"2001","journal-title":"Nat. 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