{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:39:31Z","timestamp":1790710771879,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tirzepatide (TZP), the first approved dual glucagon\u2010like peptide 1 (GLP\u20101)\/glucose\u2010dependent insulinotropic polypeptide (GIP) agonist, has shown neuroprotective effects in preclinical models and early observational studies. This review maps and appraises current preclinical and clinical evidence on TZP's potential neuroprotective effects in neurodegenerative diseases (Alzheimer's and Parkinson's disease), neuroinflammation, cerebrovascular outcomes, neurovestibular disorders, brain tumor response, and idiopathic intracranial hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Scopus, Web of Science, Embase, and Elton B. Stephens Company (EBSCO) were searched through September 30, 2025. Eligible sources included original preclinical or clinical studies reporting neurological or neuroprotective effects of TZP. Quality was assessed using SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) and Collaborative Approach to Meta\u2010Analysis and Review of Animal Data from Experimental Studies (CAMARADE) for in vivo studies, toxicological data reliability assessment tool (ToxRTool) for in vitro, Newcastle\u2010Ottawa scale (NOS) for cohorts, and Joanna Briggs Institute (JBI) for case reports.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010two studies met inclusion criteria as follows: 11 preclinical investigations, 3 retrospective cohorts, and 8 case reports. Preclinical studies demonstrated mitochondrial stabilization (adenosine triphosphate [ATP] restoration; PINK1\/Parkin), anti\u2010oxidative and anti\u2010inflammatory signaling, synaptic support (PSD\u201095\/synaptophysin), and blood\u2013brain barrier reinforcement (claudin\u20101), alongside behavioral improvements. Retrospective cohorts reported reduced cerebrovascular and neurodegenerative disease incidence, papilledema, and headaches, though one cohort identified higher risk of central vertigo and vestibular neuronitis. Case reports documented compression neuropathies, autoimmune encephalitis, hypoglycemia\u2010related seizures, psychiatric reactions, and rhabdomyolysis, most resolving with dose adjustment or discontinuation. Risk\u2010of\u2010bias appraisal revealed frequent \u201cunclear\u201d ratings in animal studies, \u201creliable with restrictions\u201d in vitro, and high NOS scores for cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TZP exhibits biologically plausible neuroprotective mechanisms preclinically. Prospective trials with standardized neurological endpoints, active\u2010comparator designs, and structured safety monitoring are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71702","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:45:59Z","timestamp":1787031959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Neuroprotective Potentials of Dual GIP\/GLP1\u2010RA (Tirzepatide): From Preclinical Experiments to Clinical Trials: A Scoping Review"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0361-4609","authenticated-orcid":false,"given":"Yousef","family":"Hawas","sequence":"first","affiliation":[{"name":"Faculty of Medicine Tanta University  Tanta Egypt"},{"name":"Medical Research Group of Egypt  Arlington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8917-671X","authenticated-orcid":false,"given":"Mohamed","family":"Abouzid","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmacy and Pharmacokinetics Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5802-2291","authenticated-orcid":false,"given":"Ahmed Farid","family":"Gadelmawla","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt  Arlington Massachusetts USA"},{"name":"Faculty of Medicine Menoufia University  Shebin El\u2010Kom Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4300-8113","authenticated-orcid":false,"given":"Dalia Kamal","family":"Ewis","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt  Arlington Massachusetts USA"},{"name":"Faculty of Medicine Beni Suef University  Beni Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8299-6945","authenticated-orcid":false,"given":"Abdallah","family":"Khatatbeh","sequence":"additional","affiliation":[{"name":"Al\u2010Hussein Medical Center Jordanian Royal Medical Services  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4018-8146","authenticated-orcid":false,"given":"Yasmin","family":"Negida","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Zagazig University  Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5363-6369","authenticated-orcid":false,"given":"Ahmed","family":"Negida","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt  Arlington Massachusetts USA"},{"name":"Department of Neurology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"issue":"8","key":"e_1_2_13_2_1","first-page":"2001","article-title":"Epilepticus Secondary to Tirzepatide Induced Severe Hypoglycemia: A Case Report","volume":"7","author":"Parikh A.","year":"2024","journal-title":"Mega Journal of Case Reports"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.japh.2025.102474"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S525690"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13962"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/1364557032000119616"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.01.013"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.70019"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdnut.2024.102316"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1660785"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0972"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1262\u20103636(08)73398\u20106"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.105065"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(26)00459\u20109"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000212661"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.4c00729"},{"key":"e_1_2_13_17_1","unstructured":"Duke University.2025.A Phase IV Placebo\u2010Controlled Single Center Trial for Tirzepatide in Idiopathic Intracranial Hypertension Trial (TIIHT) Clinical Trial Registration NCT07191873.clinicaltrials.gov."},{"key":"e_1_2_13_18_1","unstructured":"U.S. Food and Drug Administration. 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