{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:28:51Z","timestamp":1791260931696,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":407,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Parkinson's disease (PD) is, to a large extent, specific to the human species. Most symptoms are the consequence of the preferential degeneration of the dopamine\u2010synthesizing cells of the mesostriatal\u2010mesocortical neuronal pathway. Reasons for that can be traced back to the evolutionary mechanisms that shaped the dopamine neurons in humans. In vertebrates, dopamine\u2010containing neurons and nuclei do not exhibit homogenous phenotypes. In this respect, mesencephalic dopamine neurons of the substantia nigra and ventral tegmental area are characterized by a molecular combination (tyrosine hydroxylase, aromatic amino acid decarboxylase, monoamine oxidase, vesicular monoamine transporter, dopamine transporter\u2014to name a few), which is not found in other dopamine\u2010containing neurons of the vertebrate brain. In addition, the size of these mesencephalic DA nuclei is tremendously expanded in humans as compared to other vertebrates. Differentiation of the mesencephalic neurons during development depends on genetic mechanisms, which also differ from those of other dopamine nuclei. In contrast, pathophysiological approaches to PD have highlighted the role of ubiquitously expressed molecules such as a\u2010synuclein, parkin, and microtubule\u2010associated proteins. We propose that the peculiar phenotype of the dopamine mesencephalic neurons, which has been selected during vertebrate evolution and reshaped in the human lineage, has also rendered these neurons particularly prone to oxidative stress, and thus, to the fairly specific neurodegeneration of PD. Numerous evidence has been accumulated to demonstrate that perturbed regulation of DAT\u2010dependent dopamine uptake, DAT\u2010dependent accumulation of toxins, dysregulation of TH activity as well as high sensitivity of DA mesencephalic neurons to oxidants are key components of the neurodegeneration process of PD. This view points to the contribution of nonspecific mechanisms (\u03b1\u2010synuclein aggregation) in a highly specific cellular environment (the dopamine mesencephalic neurons) and provides a robust framework to develop novel and rational therapeutic schemes in PD.<\/jats:p>","DOI":"10.1196\/annals.1332.015","type":"journal-article","created":{"date-parts":[[2005,1,29]],"date-time":"2005-01-29T01:15:36Z","timestamp":1106961336000},"page":"231-249","source":"Crossref","is-referenced-by-count":69,"title":["The Degeneration of Dopamine Neurons in Parkinson's Disease: Insights from Embryology and Evolution of the Mesostriatocortical System"],"prefix":"10.1111","volume":"1035","author":[{"given":"PHILIPPE","family":"VERNIER","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FREDERIC","family":"MORET","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SOPHIE","family":"CALLIER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARINA","family":"SNAPYAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHRISTOPHE","family":"WERSINGER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANITA","family":"SIDHU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,12]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196702162760703"},{"key":"e_1_2_8_4_2","unstructured":"Przedborski S. V. Kostic N. Giladi et al.2003. Dopaminergic systems in Parkinson's disease in dopamine receptors and transporters. A. Sidhu M. Laruelle & P. Vernier Eds.: 363\u2013402. Marcel Dekker. New York."},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(02)00161-4"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/1071576021000016535"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/420539"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01485901"},{"key":"e_1_2_8_10_2","first-page":"593","article-title":"Les l\u00e9sions anatomiques de la Maladie de Parkinson","volume":"28","author":"Foix M.","year":"1921","journal-title":"Rev. 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