{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:01:52Z","timestamp":1791900112095,"version":"4.3.4"},"reference-count":87,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Irisin is a hormone cleaved from fibronectin type\u2010III domain\u2010containing protein 5 in response to exercise and may be therapeutic in Alzheimer's disease (AD). Irisin is shown to repair damage caused by midlife cardiometabolic risk factors for AD (i.e., diabetes mellitus; hypertension), prevent neural amyloid beta aggregation and reduce neuroinflammation. However, there are no investigations of irisin's effect on AD\u2010associated tauopathy in the brain. This study begins to address this gap in knowledge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transgenic htau mice that selectively develop age\u2010related tauopathy were treated with recombinant irisin (100\u00a0\u00b5g\/kg weekly i.p.) beginning at a pre\u2010symptomatic age (4\u00a0months) to determine if irisin could prevent emergence of early neuropathology. One month later, mice were sacrificed to collect brain tissue and serum. Protein levels of ptau (serine 202), inflammatory cytokine tumour necrosis factor alpha (TNF\u03b1) and FNDC5 were quantified using capillary\u2010based western blotting (Wes).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our data show that irisin treatment significantly reduced ptau and TNF\u03b1 in the hippocampus and serum of female htau mice compared to vehicle\u2010treated controls. Irisin treatment did not alter ptau levels in male htau hippocampus and appeared to enhance both neural and systemic TNF\u03b1 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides the first evidence that enhancing the endogenous hormone irisin may be therapeutic against emerging neuropathology in a tauopathy\u2010selective AD model. This is important because there are currently no disease\u2010modifying therapeutics available for AD, and few agents in development address the multiple disease targets irisin appears to\u2014making irisin an intriguing therapeutic candidate for further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12711","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T03:47:17Z","timestamp":1616730437000},"page":"967-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre\u2010symptomatic female but not male htau mice"],"prefix":"10.1111","volume":"47","author":[{"given":"Katie A.","family":"Bretland","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University  Rootstown OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University  Rootstown OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly M.","family":"Bretland","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University  Rootstown OH USA"},{"name":"Kent State University  Kent OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University  Rootstown OH USA"},{"name":"Akron Children's Hospital Rebecca D. 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