{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:04:41Z","timestamp":1787025881925,"version":"build-2736575974"},"reference-count":37,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T00:00:00Z","timestamp":1522108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2018,3,27]]},"abstract":"<jats:p>Alzheimer\u2019s disease is characterized by abnormal amyloid-\u03b2 (A\u03b2) peptide accumulation beginning decades before symptom onset. An effective prophylactic treatment aimed at arresting the amyloidogenic pathway would therefore need to be initiated prior to the occurrence of A\u03b2 pathology. The SIGMAR1 gene encodes a molecular chaperone that modulates processing of the amyloid-\u03b2 protein precursor (A\u03b2PP). Fluvoxamine is a selective serotonin reuptake inhibitor and a potent SIGMAR1 agonist. We therefore hypothesized that fluvoxamine treatment would reduce A\u03b2 production and improve cognition. We firstly investigated the impact of SIGMAR1 on A\u03b2PP processing, and found that overexpression and knockdown of SIGMAR1 significantly affected \u03b3-secretase activity in SK-N-MC neuronal cells. We then tested the impact of fluvoxamine on A\u03b2 production in an amyloidogenic cell model, and found that fluvoxamine significantly reduced A\u03b2 production by inhibiting \u03b3-secretase activity. Finally, we assessed the efficacy of long-term treatment (i.e., \u223c8 months) of 10\u200amg\/kg\/day fluvoxamine in the J20 amyloidogenic mouse model; the treatment was initiated prior to the occurrence of predicted A\u03b2 pathology. Physical examination of the animals revealed no overt pathology or change in weight. We conducted a series of behavioral tests to assess learning and memory, and found that the fluvoxamine treatment significantly improved memory function as measured by novel object recognition task. Two other tests revealed no significant change in memory function. In conclusion, fluvoxamine has a clear impact on \u03b3-secretase activity and A\u03b2PP processing to generate A\u03b2, and may have a protective effect on cognition in the J20 mice.<\/jats:p>","DOI":"10.3233\/jad-171001","type":"journal-article","created":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T05:23:33Z","timestamp":1522214613000},"page":"1777-1787","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Effect of Fluvoxamine on Amyloid-\u03b2 Peptide Generation and Memory"],"prefix":"10.1177","volume":"62","author":[{"given":"Woojin Scott","family":"Kim","sequence":"first","affiliation":[{"name":"Neuroscience Research Australia, Sydney, NSW, Australia"},{"name":"School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia"},{"name":"The University of Sydney \u2013 Brain and Mind Centre, Sydney, NSW, 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