{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:01:30Z","timestamp":1773309690631,"version":"3.50.1"},"reference-count":95,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["W\u2010de.NBI\u2010005"],"award-info":[{"award-number":["W\u2010de.NBI\u2010005"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014690","name":"Ministerium f\u00fcr Kultur und Wissenschaft des Landes Nordrhein-Westfalen","doi-asserted-by":"publisher","award":["111.08.03.05\u2013133974"],"award-info":[{"award-number":["111.08.03.05\u2013133974"]}],"id":[{"id":"10.13039\/501100014690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017331","name":"Ministerium f\u00fcr Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen","doi-asserted-by":"publisher","award":["233\u20131.08.03.03\u2013031"],"award-info":[{"award-number":["233\u20131.08.03.03\u2013031"]}],"id":[{"id":"10.13039\/100017331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017331","name":"Ministerium f\u00fcr Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen","doi-asserted-by":"publisher","award":["\u2011"],"award-info":[{"award-number":["\u2011"]}],"id":[{"id":"10.13039\/100017331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017331","name":"Ministerium f\u00fcr Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen","doi-asserted-by":"publisher","award":["68079"],"award-info":[{"award-number":["68079"]}],"id":[{"id":"10.13039\/100017331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advanced Biology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Physiological aging is accompanied by structural and molecular changes in the brain, with varying degrees in different brain areas, and is considered one of the major risk factors for neurodegenerative diseases. Thus, the present study focuses on elucidating age\u2010related changes in the substantia nigra pars compacta (SNpc), a brain region particularly vulnerable in Parkinson's disease. Here, the aim is to gain a spatially resolved view of aging\u2010dependent alterations to conclude early processes potentially involved in neurodegeneration. Neuromelanin granules and SNpc tissue are isolated from tissue samples of young and elderly individuals via laser microdissection and measured by mass spectrometry to ascertain changes in protein expression in response to age. The findings include the identification of reduced levels of proteins involved in dopaminergic neurotransmission, either suggesting a specific loss of dopaminergic neurons or a reduction in metabolic activity. Furthermore, increased neuroinflammation is observed in elderly individuals and alterations in vesicular trafficking as well as mitochondrial proteins. Consequently, this exploratory study suggests that alterations causing known pathomechanisms of Parkinson's disease are already occurring in the physiological aging process. Since aging is still the most important risk factor for neurodegenerative diseases, these findings strengthen the necessity for studying age\u2010related changes.<\/jats:p>","DOI":"10.1002\/adbi.202500358","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T08:59:28Z","timestamp":1758185968000},"source":"Crossref","is-referenced-by-count":0,"title":["A Spatially Resolved View on the Aging Substantia nigra: An Exploratory Proteomic Study"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-4631","authenticated-orcid":false,"given":"Britta","family":"Eggers","sequence":"first","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Hausherr","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Lim","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Schork","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"},{"name":"Core Unit for Bioinformatics (CUBiMed.RUB), Medical Faculty Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bilhan","family":"Karacora","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Grugel","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Eisenacher","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"},{"name":"Core Unit for Bioinformatics (CUBiMed.RUB), Medical Faculty Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel Gil","family":"Aldea","sequence":"additional","affiliation":[{"name":"Navarrabiomed Biobank, Hospital Universitario de Navarra  Pamplona 31008 Navarra Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Riederer","sequence":"additional","affiliation":[{"name":"University Hospital Wuerzburg, Center of Mental Health, Clinic and Policlinic for Psychiatry Psychosomatics and Psychotherapy  Margarete\u2010Hoeppel\u2010Platz 1 D\u201097080 Wuerzburg Germany"},{"name":"Psychiatry Department of Clinical Research University of Southern Denmark Odense University Hospital  Odense C 5000 Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Gerlach","sequence":"additional","affiliation":[{"name":"Center of Mental Health Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg University of Wuerzburg  97080 Wuerzburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Marcus","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom\u2010Center Medical Faculty Ruhr University Bochum  44801 Bochum Germany"},{"name":"Medical Proteome Analysis, Center for Proteindiagnostics (PRODI) Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.2005.036665"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.01.077"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-021-02331-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.38.8.1285"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.683459"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0221-2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1989.tb01778.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pbr.2020.02.005"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0643-3_8"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2741\/E591"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-018-0050-8"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2005.02.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-021-02414-z"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0250-5"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.08.024"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2751com"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08858-y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27776"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-006-0449-y"},{"key":"e_1_2_11_21_1","first-page":"R37","volume":"234","author":"Eggers B.","year":"2025","journal-title":"Adv. Biol."},{"key":"e_1_2_11_22_1","volume":"178","author":"Wulf M.","year":"2021","journal-title":"J. Vis. Exp."},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-022-02530-4"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11223538"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158689"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001037"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21277"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx172"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu178"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-018-0063-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.06.051"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.05.012"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86847-2"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1011"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baz031"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.09.014"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-024-01770-7"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-024-04117-y"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00013"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2017.02.009"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00317-6"},{"key":"e_1_2_11_42_1","doi-asserted-by":"crossref","unstructured":"N.Eriksen A. K.Stark B.Pakkenberg in Birth Life and Death of Dopaminergic Neurons in the Substantia Nigra Journal of Neural Transmission. Supplementa Springer Vienna Austria2009 pp.203\u2013213.","DOI":"10.1007\/978-3-211-92660-4_16"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13031"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.08.021"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt192"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13607"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-023-02723-5"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.878771"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00684-6"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.2742"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa269"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-16-06142.1997"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64538-5"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-100162"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005503"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glx135"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09703"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(96)00016-1"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-12-141"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4169575"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.027"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1179401"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909814117"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.01.031"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.04.066"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.745394"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1162"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.11.017"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1809592"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0222-5"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03565-0"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.12.008"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201744722"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12189"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06726-w"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18413"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118876"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10432-5"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1602-2"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-56"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-018-0914-7"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.12.014"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20209596"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04295-4"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425"},{"key":"e_1_2_11_86_1","first-page":"112","volume":"21","author":"Xu J.","year":"2000","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1153251"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.12.005"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076354"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1011"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_11_94_1","volume-title":"R: A Language and Environment for Statistical Computing_. R Foundation for Statistical Computing","author":"R Core Team","year":"2025"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"}],"container-title":["Advanced Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adbi.202500358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adbi.202500358","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adbi.202500358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T15:49:44Z","timestamp":1773244184000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adbi.202500358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":95,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/adbi.202500358"],"URL":"https:\/\/doi.org\/10.1002\/adbi.202500358","archive":["Portico"],"relation":{},"ISSN":["2701-0198","2701-0198"],"issn-type":[{"value":"2701-0198","type":"print"},{"value":"2701-0198","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"article-number":"e00358"}}