{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:40:03Z","timestamp":1791690003101,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transthyretin (TTR) amyloidogenesis involves the formation, aggregation, and deposition of amyloid fibrils from tetrameric TTR in different organs and tissues. While the result of amyloidoses is the accumulation of amyloid fibrils resulting in end-organ damage, the nature, and sequence of the molecular causes leading to amyloidosis may differ between the different variants. In addition, fibril accumulation and toxicity vary between different mutations. Structural changes in amyloidogenic TTR have been difficult to identify through X-ray crystallography; but nuclear magnetic resonance spectroscopy has revealed different chemical shifts in the backbone structure of mutated and wild-type TTR, resulting in diverse responses to the cellular conditions or proteolytic stress. Toxic mechanisms of TTR amyloidosis have different effects on different tissues. Therapeutic approaches have evolved from orthotopic liver transplants to novel disease-modifying therapies that stabilize TTR tetramers and gene-silencing agents like small interfering RNA and antisense oligonucleotide therapies. The underlying molecular mechanisms of the different TTR variants could be responsible for the tropisms to specific organs, the age at onset, treatment responses, or disparities in the prognosis.<\/jats:p>","DOI":"10.3390\/ijms222313158","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"13158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["A Brief Journey through Protein Misfolding in Transthyretin Amyloidosis (ATTR Amyloidosis)"],"prefix":"10.3390","volume":"22","author":[{"given":"Alejandra","family":"Gonzalez-Duarte","sequence":"first","affiliation":[{"name":"Departamento de Neurolog\u00eda, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Vasco de Quiroga 15, Col. Belisario Dominguez Secci\u00f3n XV, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-3886","authenticated-orcid":false,"given":"Alfredo","family":"Ulloa-Aguirre","sequence":"additional","affiliation":[{"name":"Red de Apoyo a la Investigaci\u00f3n, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1007\/s00415-017-8708-4","article-title":"Transthyretin familial amyloid polyneuropathy: An update","volume":"265","year":"2018","journal-title":"J. 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