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We examined the involvement of autophagy in levodopa (\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa)\u2010induced dyskinesia, a frequent motor complication developed in response to standard dopamine replacement therapy in parkinsonian patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used mouse and non\u2010human primate models of Parkinson's disease to examine changes in autophagy associated with chronic\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa administration and to establish a causative link between impaired autophagy and dyskinesia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010induced dyskinesia is associated with accumulation of the autophagy\u2010specific substrate p62, a marker of autophagy deficiency. Increased p62 was observed in a subset of projection neurons located in the striatum and depended on\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010mediated activation of dopamine D1 receptors, and mammalian target of rapamycin. Inhibition of mammalian target of rapamycin complex 1 with rapamycin counteracted the impairment of autophagy produced by\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa, and reduced dyskinesia. The anti\u2010dyskinetic effect of rapamycin was lost when autophagy was constitutively suppressed in D1 receptor\u2010expressing striatal neurons, through inactivation of the autophagy\u2010related gene protein 7.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings indicate that augmented responsiveness at D1 receptors leads to dysregulated autophagy, and results in the emergence of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010induced dyskinesia. They further suggest the enhancement of autophagy as a therapeutic strategy against dyskinesia. \u00a9 2021 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.28480","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T13:45:47Z","timestamp":1610977547000},"page":"1137-1146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Involvement of Autophagy in Levodopa\u2010Induced Dyskinesia"],"prefix":"10.1002","volume":"36","author":[{"given":"Michael","family":"Feyder","sequence":"first","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Plewnia","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ori J.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Pharmacology and Psychiatry Columbia University, and New York State Psychiatric Institute  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Spigolon","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Piccin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Urbina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-9045","authenticated-orcid":false,"given":"Benjamin","family":"Dehay","sequence":"additional","affiliation":[{"name":"Univ. 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