{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:01:56Z","timestamp":1778194916825,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Familial amyloidotic polyneuropathy is an autosomal dominant disorder mainly characterized by the extracellular deposition of transthyretin, with special involvement of the peripheral nerve. Several animal models have been generated, including transgenic mice carrying the most prevalent TTR mutation (TTR Val30Met). TTR\u2010Val30Met mice without endogenous TTR (TTR\u2010Val30Met X TTR\u2010KO) were previously analyzed in our laboratory and \u223c60% of the animals over 1 year of age were found to have deposition as amyloid, i.e., with Congo red (CR) \u2010positive material, constituting a good tool to investigate the effect of drugs on TTR deposition and fibrillogenesis. We recently showed that the drug doxycycline acts in vitro as a TTR fibril disrupter. In the present work we assessed the activity of this drug in vivo in the TTR\u2010Met30Val X TTR\u2010KO mice. Doxycycline was administrated in the drinking water to 23\u2010to 28\u2010month\u2010old mice over a period of 3 months. Immunohistochemistry analyses revealed no differences in nonfibrillar TTR deposition between treated (\n                    <jats:italic>n<\/jats:italic>\n                    =11) and untreated mice (\n                    <jats:italic>n<\/jats:italic>\n                    =11). However, CR\u2010positive material was observed only in the control group (untreated) whereas none of the animals treated with doxycycline was CR\u2010positive. Immunohistochemistry for several markers associated with amyloid, such as matrix metalloproteinase\u20109 (MMP\u20109) and serum amyloid P component (SAP), was performed. MMP\u20109 was altered with significantly lower levels in treated animals compared with the control group. Mouse SAP was absent in treated animals, being observed only in untreated animals presenting TTR congophilic deposits. These results indicate that doxycycline is capable of disrupting TTR CR\u2010positive amyloid deposits and decreases standard markers associated with fibrillar deposition, being a potential drug in the treatment of amyloidosis.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, 234\u2013239 (2005)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-4509com","type":"journal-article","created":{"date-parts":[[2006,1,31]],"date-time":"2006-01-31T19:58:03Z","timestamp":1138737483000},"page":"234-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model"],"prefix":"10.1096","volume":"20","author":[{"given":"I.","family":"Cardoso","sequence":"first","affiliation":[{"name":"Molecular Neurobiology Unit IBMC  Porto Portugal"}]},{"given":"M. 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