{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:20:07Z","timestamp":1792153207053,"version":"4.4.0"},"reference-count":170,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nigrostriatal dopaminergic systems govern physiological functions related to locomotion, and their dysfunction leads to movement disorders, such as Parkinson\u2019s disease and dopa-responsive dystonia (Segawa disease). Previous studies revealed that expression of the gene encoding nigrostriatal tyrosine hydroxylase (TH), a rate-limiting enzyme of dopamine biosynthesis, is reduced in Parkinson\u2019s disease and dopa-responsive dystonia; however, the mechanism of TH depletion in these disorders remains unclear. In this article, we review the molecular mechanism underlying the neurodegeneration process in dopamine-containing neurons and focus on the novel degradation pathway of TH through the ubiquitin-proteasome system to advance our understanding of the etiology of Parkinson\u2019s disease and dopa-responsive dystonia. We also introduce the relation of \u03b1-synuclein propagation with the loss of TH protein in Parkinson\u2019s disease as well as anticipate therapeutic targets and early diagnosis of these diseases.<\/jats:p>","DOI":"10.3390\/ijms21113779","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T05:35:52Z","timestamp":1590557752000},"page":"3779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson\u2019s Disease and Dopa-Responsive Dystonia"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-7847","authenticated-orcid":false,"given":"Ichiro","family":"Kawahata","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-2824","authenticated-orcid":false,"given":"Kohji","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1176\/jnp.14.2.223","article-title":"An essay on the shaking palsy. 1817","volume":"14","author":"Parkinson","year":"2002","journal-title":"J. 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