{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:14:56Z","timestamp":1788178496370,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neurodegeneration presents a significant challenge in ageing populations, often being detected too late for effective intervention. Biomarkers have shown great potential in addressing this issue, with neurofilament (Nf) proteins emerging as validated biomarkers presently transitioning from research to routine laboratory use. Whilst advances in large\u2010scale quantitative analyses have enabled the targeted study of proteolytic Nf fragments in blood, the complete landscape of the Nf proteolytic breakdown remains unknown. This study presents a comprehensive atlas of the human Nf isoform (\n                    <jats:italic>Z<\/jats:italic>\n                    ) degradome, based on the number of known cleavage sites (\n                    <jats:italic>x<\/jats:italic>\n                    ). The full scale of the Nf degradome is described by the formula:\n                    <jats:italic>Z<\/jats:italic>\n                    \u2009=\u2009((\n                    <jats:italic>x<\/jats:italic>\n                    \u2009+\u20091)\u2009\u00d7\u2009(\n                    <jats:italic>x<\/jats:italic>\n                    \u2009+\u20092)\/2)\u2009\u2212\u20091. The resulting neurofilament degradome atlas (NDA) was validated through a triple\u2010layer approach using in\u00a0vitro data (open access at:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.5522\/04\/25689378.v1\">https:\/\/doi.org\/10.5522\/04\/25689378.v1<\/jats:ext-link>\n                    ). The NDA offers valuable applications in biomarker detection, targeted antibody development, exploration of autoimmunity and understanding Nf aggregate formation. Analysis of the Nf degradome reveals novel insights into neurodegenerative diseases by investigating peptide pools affected by genetic mutations in the Nf genome and alterations in proteolytic pathways. The annotated NDA is publicly available as a database resource, supporting advancements in affinity\u2010based biomarker tests through informed peptide selection and minimising biases in label\u2010free approaches. In conclusion, this study highlights the biological significance of a dynamic pool of coexisting proteolytic Nf peptides, providing a framework that can be applied to other proteins.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70023-fig-0012-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70023","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:48:50Z","timestamp":1741740530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteolysis\u2010Based Biomarker Repertoire of the Neurofilament Proteome"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-9749","authenticated-orcid":false,"given":"Axel","family":"Petzold","sequence":"first","affiliation":[{"name":"Queen Square Institute of Neurology, UCL and The National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90639-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-022-01019-y"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.07.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.7b00488"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006435"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2003.01228.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2020.10.011"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac045"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201010\u2010421"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00010.2003"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16261"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","unstructured":"Ding E. 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