{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:53:49Z","timestamp":1781855629766,"version":"3.54.5"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) is the most common cause of dementia. Pleiotrophin (PTN) is a neurotrophic factor relevant for central nervous system repair, neuron differentiation and survival. It is upregulated in different neuroinflammatory conditions. PTN is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) \u03b2\/\u03b6. In a previous study, we showed that a short treatment with the RPTP\u03b2\/\u03b6 inhibitor MY10 reduced amyloid beta (A\u03b2) plaque formation and glial activation in old APP\/PS1 mice. Nevertheless, these preliminary data required new studies to prove the disease-modifying potential of RPTP\u03b2\/\u03b6 inhibition by using younger animals and a longer treatment with MY10. Thus, we have now treated for 3 months five- to seven-month-old wild type (WT) and APP\/PS1 mice with MY10. This treatment decreased A\u03b2 plaque formation and increased the number of microglial cells in the dorsal subiculum of APP\/PS1 mice. In addition, MY10 reduced the number of GFAP+, not Iba1+, cells surrounding A\u03b2 plaques. As expected, PTN expression was upregulated in the brain of APP\/PS1 compared to WT mice and it was mainly found in Iba1+ and GFAP+ cells. Interestingly, treatment with MY10 significantly decreased the expression of PTN and the number of PTN-expressing Iba1+ and GFAP+ cells. MY10 induced a significant decrease of\n                    <jats:italic>Mmp9<\/jats:italic>\n                    expression in the hippocampus of APP\/PS1 mice, a key enzyme in AD progression. In summary, chronic inhibition of RPTP\u03b2\/\u03b6 in APP\/PS1 mice reduces A\u03b2 plaque deposition, modulating glial-plaque interactions and the expression of specific genes including\n                    <jats:italic>Ptn<\/jats:italic>\n                    and its receptor.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1839516","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:28:25Z","timestamp":1781854105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic inhibition of receptor protein tyrosine phosphatase \u03b2\/\u03b6 reduces amyloid plaque load and modulates pleiotrophin-expressing glial cells, glial-plaque interactions and genes related to amyloid beta clearance"],"prefix":"10.3389","volume":"17","author":[{"given":"Teresa","family":"Font\u00e1n-Baselga","sequence":"first","affiliation":[{"name":"Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Ca\u00f1eque-Rufo","sequence":"additional","affiliation":[{"name":"Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]},{"name":"Department of Chemistry and Biochemistry, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rivera-Illades","sequence":"additional","affiliation":[{"name":"Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Gramage","sequence":"additional","affiliation":[{"name":"Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Zapico","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"de Pascual-Teresa","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Pilar","family":"Ramos-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vicente-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Herrad\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe","place":["Boadilla del Monte, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"116989","DOI":"10.1016\/j.jns.2020.116989","article-title":"Influence of plasma matrix metalloproteinase levels on longitudinal changes in Alzheimer's disease (AD) biomarkers and cognitive function in patients with mild cognitive impairment due to AD registered in the Alzheimer's disease neuroimaging initiative database","volume":"416","author":"Abe","year":"2020","journal-title":"J. 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