{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:01:41Z","timestamp":1773025301338,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease (MND) characterized by progressive degeneration of both upper and lower motor neurons, along with skeletal muscles innervated by them. The identification of key molecules involved in disease pathology remains crucial for ALS, as no curative treatment is currently available. Pleiotrophin (PTN) and midkine (MK) are closely related, heparin\u2010binding cytokines with overlapping effects. These molecules have been shown to be neuroprotective by modulating neuroinflammation, supporting neuronal survival, growth, and differentiation, and enhancing synaptic strength and plasticity. Despite their reported neuroprotective properties, the involvement of PTN and MK signaling in ALS has not been previously investigated. In this study, we characterized the expression of the PTN\/MK pathway in the lumbar spinal cords (SCs) of TDP\u201043\n                    <jats:sup>A315T<\/jats:sup>\n                    mice across different disease stages. We report a significant upregulation of\n                    <jats:italic>Ptn<\/jats:italic>\n                    ,\n                    <jats:italic>Mdk<\/jats:italic>\n                    , and its receptor protein tyrosine phosphatase zeta (\n                    <jats:italic>Ptprz1<\/jats:italic>\n                    ) mRNA levels at end\u2010stage of disease in the lumbar SC of TDP\u201043\n                    <jats:sup>A315T<\/jats:sup>\n                    mice compared with age\u2010matched wild\u2010type littermates. Protein levels of PTN and MK were also upregulated at end\u2010stage of disease. By immunofluorescence analysis, we also observed an upregulation of the immunostaining of both cytokines in neurons, astrocytes, microglia, and pericytes\u2010like structures at end\u2010stage of disease in the SC of TDP\u201043\n                    <jats:sup>A315T<\/jats:sup>\n                    mice. These findings open a new avenue to further study the potential role of the PTN\/MK signaling axis in the pathogenesis of ALS.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Animal Ethics Committee of the Hospital Nacional de Parapl\u00e9jicos in Toledo (Spain): Approval No. 26\/OH 2018\n                  <\/jats:p>","DOI":"10.1111\/neup.70044","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:25:40Z","timestamp":1769646340000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pleiotrophin\/Midkine Pathway Is Dysregulated in a\n                    <scp>TDP<\/scp>\n                    \u2010\n                    <scp>\n                      43\n                      <sup>A315T<\/sup>\n                    <\/scp>\n                    Mouse Model of Amyotrophic Lateral Sclerosis (\n                    <scp>ALS<\/scp>\n                    )"],"prefix":"10.1111","volume":"46","author":[{"given":"Paloma","family":"Mart\u00ednez\u2010Ales\u00f3n","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Farmac\u00e9uticas y de la Salud, Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe  Madrid Spain"},{"name":"Instituto Universitario de Estudios de Las Adicciones, Universidad San Pablo\u2010CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Benito\u2010Casado","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Farmac\u00e9uticas y de la Salud, Facultad de Farmacia Universidad San Pablo\u2010CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe  Madrid 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