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It is currently explored as a therapeutic target for Alzheimer's disease (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>) and cancer. Mechanism\u2010based toxicity needs to be thoroughly evaluated for \u03b3\u2010secretase inhibitory and\/or modulatory drugs. This study comparatively assessed putative \u03b3\u2010secretase catalytic sites in rat peripheral tissues relative to brain and explored an effort of its pharmacological inhibition on hair regeneration. Using [<jats:sup>3<\/jats:sup>H]\u2010labelled L685,458, a potent \u03b3\u2010secretase inhibitor, as probe, we found more abundant presence of \u03b3\u2010secretase binding sites in the liver, gastrointestinal tract, hair follicle, pituitary gland, ovary and testis, as compared to the brain. Local application of L658,458 delayed vibrissal regrowth following whisker removal. These results suggest that \u03b3\u2010secretase may execute important biological functions in many peripheral systems, as in the brain. The development of \u03b3\u2010secretase inhibitors\/modulators for <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> and cancer therapy should include close monitoring of toxicological panels for hepatic, gastrointestinal, endocrinal and reproductive functions.<\/jats:p>","DOI":"10.1111\/bcpt.12271","type":"journal-article","created":{"date-parts":[[2014,5,26]],"date-time":"2014-05-26T07:02:36Z","timestamp":1401087756000},"page":"518-526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["[<sup>3<\/sup>H]\u2010L685,458 Binding Sites are Abundant in Multiple Peripheral Organs in Rats: Implications for Safety Assessment of Putative \u03b3\u2010Secretase Targeting Drugs"],"prefix":"10.1111","volume":"115","author":[{"given":"Zhi\u2010Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology Central South University School of Basic Medical Science Changsha 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