{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:29:21Z","timestamp":1790278161888,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["FTLDc 01GI1007A"],"award-info":[{"award-number":["FTLDc 01GI1007A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation of the state Baden-W\u00fcrttemberg","award":["D.3830"],"award-info":[{"award-number":["D.3830"]}]},{"name":"PreFrontALS","award":["01ED1512"],"award-info":[{"award-number":["01ED1512"]}]},{"name":"Genfi-Prox","award":["01ED2008A"],"award-info":[{"award-number":["01ED2008A"]}]},{"name":"German Research Foundation\/DFG","award":["SFB1279"],"award-info":[{"award-number":["SFB1279"]}]},{"name":"Boehringer Ingelheim Ulm University BioCenter","award":["D.5009"],"award-info":[{"award-number":["D.5009"]}]},{"DOI":"10.13039\/100009281","name":"Fondation Thierry Latran","doi-asserted-by":"publisher","award":["D.2468"],"award-info":[{"award-number":["D.2468"]}],"id":[{"id":"10.13039\/100009281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008977","name":"Universit\u00e4t Ulm","doi-asserted-by":"publisher","award":["Bausteinprogramm LSBN.0123"],"award-info":[{"award-number":["Bausteinprogramm LSBN.0123"]}],"id":[{"id":"10.13039\/501100008977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Proenkephalin (PENK) and prodynorphin (PDYN) are peptides mainly produced by the striatal medium spiny projection neurons (MSNs) under dopaminergic signaling. Therefore, they may represent candidate biomarkers in Huntington\u2019s disease (HD) and Parkinson\u2019s disease (PD), two neurodegenerative diseases characterized by striatal atrophy and\/or dysfunction.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using an in-house established liquid chromatography\u2212tandem mass spectrometry (LC\u2013MS\/MS) method in multiple reaction monitoring mode (MRM) we measured cerebrospinal fluid (CSF) levels of PENK- and PDYN- derived peptides in patients with HD (<jats:italic>n<\/jats:italic>\u2009=\u200947), PD (<jats:italic>n<\/jats:italic>\u2009=\u200961), Alzheimer\u2019s disease (<jats:italic>n<\/jats:italic>\u2009=\u200911), amyotrophic lateral sclerosis (<jats:italic>n<\/jats:italic>\u2009=\u200914) and in 92 control subjects. Moreover, we investigated the possible associations between biomarkers and disease severity scales in HD and PD and the effect\u00a0of\u00a0dopaminergic therapy on biomarker levels\u00a0in PD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In HD, CSF PENK- and PDYN-derived peptide levels were significantly decreased compared to all other groups and were associated with disease severity scores. In PD, both biomarkers were within the normal range, but higher PDYN levels were found in dopamine-treated compared to untreated patients. In PD, both CSF PENK and PDYN\u00a0did not correlate with clinical severity scales.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>CSF PENK- and PDYN-derived peptides appeared to be promising pathogenetic and disease severity markers in HD, reflecting the ongoing striatal neurodegeneration along with the loss of MSNs. In PD patients, CSF\u00a0PDYN showed a limitative role as a possible pharmacodynamic marker during dopaminergic therapy, but further investigations are needed.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-022-11187-8","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T09:02:31Z","timestamp":1655974951000},"page":"5136-5143","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cerebrospinal fluid levels of proenkephalin and prodynorphin are differentially altered in Huntington\u2019s and Parkinson\u2019s disease"],"prefix":"10.1007","volume":"269","author":[{"given":"Peggy","family":"Barschke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Abu-Rumeileh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. H. D. Rami","family":"Al Shweiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Barba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Paolini Paoletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Oeckl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Steinacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Halbgebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lewerenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert Christian","family":"Ludolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg Bernhard","family":"Landwehrmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-4267","authenticated-orcid":false,"given":"Markus","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"11187_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112441","author":"VS Witzig","year":"2020","unstructured":"Witzig VS, Komnig D, Falkenburger BH (2020) Changes in striatal medium spiny neuron morphology resulting from dopamine depletion are reversible. 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J.L. received grants from EDHN, BMBF, Boehringer-Ingelheim Ulm University Biocenter (BIU), Ministry of Education and Research Baden-Wuerttemberg, CHDI, UCB, and honoraria for lectures from CHDI, Teva, German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry, all unrelated to the work presented in this paper. A.C.L. received contracts for clinical studies with AB Science, Biogen Idec, Cytokinetics, GSK, Pharam, Novartis, TauRx, Therapeutics Ltd, Teva Pharmaceuticals and received personal fees from Mitsubish, Orion Pharma, Novartis, Teva, all unrelated to the work presented in this paper. M.O. gave scientific advice to Axon, Biogen Idec, Fujirebio and Roche, all unrelated to the work presented in this paper. The other authors report no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was approved by the local Ethics Committees of Ulm University (proposal number 20\/10 and 259\/09) and University of Perugia (CER Umbria 3944\/21). The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants or their relatives gave written informed consent to participate in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard approval"}}]}}