{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:13Z","timestamp":1787026393825,"version":"build-2736575974"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder for which there is no cure. Diabetes is one of the risk factors for developing PD. Tirzepatide is a novel long-acting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist that is on the market as a treatment for diabetes. Importantly, two phase II trials in PD patients showed good effects with the GLP-1 receptor agonists Exendin-4 and Lixisenatide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We have developed a dual GLP-1\/GIP receptor agonist (DA5-CH) that can cross the blood-brain barrier (BBB) at a higher rate than Tirzepatide. Here, we tested Exendin-4, Tirzepatide and DA5-CH in the 6-OHDA-lesion rat model of PD. The drug treatment was daily (10 nmol\/kg, ip.) for 30 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DA5-CH was more effective than Tirzepatide or Exendin-4. In the substantia nigra, dopaminergic neurons were protected, with DA5-CH being most effective. Dopamine levels in the striatum were normalized by DA5-CH, while Exendin-4 was less effective, and Tirzepatide was ineffective. The inflammation response in the lesioned striatum was reduced by the drugs as shown in reduced IL-6 and TNF-\u03b1 levels, with DA5-CH being more effective than Exendin-4, and Tirzepatide showing minimal effects. Furthermore, the \u03b1-synuclein levels in the substantia nigra were reduced by DA5-CH, superior to Exendin-4 and Tirzepatide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Therefore, DA5-CH was more effective and may be a better therapeutic drug for neurodegenerative disorders such as PD compared to Tirzepatide or Exendin-4.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1825379","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:16:56Z","timestamp":1777954616000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The novel GLP-1\/GIP dual receptor agonist DA5-CH is superior to tirzepatide and exendin-4 in the 6-OHDA Parkinson rat 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