{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:49:55Z","timestamp":1773380995871,"version":"3.50.1"},"reference-count":126,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T00:00:00Z","timestamp":1584489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Norte2020, Portugal","award":["Norte-01-0145FEDER-000008- Porto Neurosciences"],"award-info":[{"award-number":["Norte-01-0145FEDER-000008- Porto Neurosciences"]}]},{"name":"Funda\u00e7\u00e3o Millennium bcp","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["CTQ2017-87637-R"],"award-info":[{"award-number":["CTQ2017-87637-R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer\u2019s disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid A\u03b2 peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics.<\/jats:p>","DOI":"10.3390\/ijms21062075","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T03:54:14Z","timestamp":1584590054000},"page":"2075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Tiago","family":"Gi\u00e3o","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Joana","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Ellen","family":"Cotrina","sequence":"additional","affiliation":[{"name":"Institut de Qu\u00edmica Avan\u00e7ada de Catalunya (I.Q.A.C.-C.S.I.C.), 08034 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-7418","authenticated-orcid":false,"given":"Jordi","family":"Quintana","sequence":"additional","affiliation":[{"name":"Research Programme on Biomedical Informatics, Universitat Pompeu Fabra (UPF IMIM), 08003 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0821-9838","authenticated-orcid":false,"given":"Jordi","family":"Llop","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guip\u00fazcoa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades respiratorias \u2013 CIBERES, 28029 Madrid, Spain"}]},{"given":"Gemma","family":"Arsequell","sequence":"additional","affiliation":[{"name":"Institut de Qu\u00edmica Avan\u00e7ada de Catalunya (I.Q.A.C.-C.S.I.C.), 08034 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-7055","authenticated-orcid":false,"given":"Isabel","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11793","DOI":"10.1016\/S0021-9258(17)39100-7","article-title":"Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat","volume":"260","author":"Soprano","year":"1985","journal-title":"J. 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