{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:10:12Z","timestamp":1783955412149,"version":"3.55.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Umea University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biomark Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Transthyretin (TTR) amyloidosis is a progressive, life-threatening disorder caused by extracellular deposition of amyloid fibrils derived from the plasma protein TTR. Inherited forms are associated with destabilizing TTR mutations; however, recent findings indicate that amyloid formation in vivo may be promoted by disulfide bond formation between TTR subunits, suggesting oxidative stress as a potential contributor to protein misfolding and disease progression. Glutathione (GSH) is a central component of the antioxidant defense system, and disruption of GSH homeostasis can lead to the accumulation of pyroglutamate (PGA), which is detectable in plasma. Moreover, oxidative stress is frequently linked to inflammation, which may be reflected by increased indoleamine 2,3-dioxygenase 1 (\n                      <jats:italic>IDO1<\/jats:italic>\n                      ) activity, observed as an elevated plasma kynurenine\/tryptophan ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma levels of PGA, kynurenine, and tryptophan were quantified by liquid chromatography-mass spectrometry in cohorts comprising healthy TTR wild-type controls, asymptomatic carriers of the TTR-V30M mutation, and symptomatic patients with TTR-V30M amyloidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Symptomatic individuals had significantly elevated plasma PGA levels compared with both asymptomatic carriers and age-matched healthy controls, consistent with impaired GSH homeostasis. In parallel, the kynurenine\/tryptophan ratio was increased in symptomatic TTR-V30M carriers, supporting inflammatory activation in manifest disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings identify disrupted GSH homeostasis and inflammatory activation as metabolic features associated with symptomatic TTR-V30M amyloidosis in vivo, supporting a link between redox imbalance and disease manifestation. Strategies aimed at restoring antioxidant homeostasis and limiting inflammatory oxidative stress may therefore warrant further investigation as approaches to delay onset or slow disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40364-026-00970-8","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T10:35:55Z","timestamp":1783766155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disrupted glutathione homeostasis in the pathogenesis of TTR-V30M amyloidosis"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3137-9266","authenticated-orcid":false,"given":"Anushree","family":"Bachhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Johannson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melisnur","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1019-3367","authenticated-orcid":false,"given":"Sanduni","family":"Jayaweera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5300-6487","authenticated-orcid":false,"given":"Malin","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-7643","authenticated-orcid":false,"given":"Intissar","family":"Anan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8743-8720","authenticated-orcid":false,"given":"Anders","family":"Olofsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"issue":"1","key":"970_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1172\/JCI111390","volume":"74","author":"MJ Saraiva","year":"1984","unstructured":"Saraiva MJ, Birken S, Costa PP, Goodman DS. Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. Definition of molecular abnormality in transthyretin (prealbumin). J Clin Invest. 1984;74(1):104\u201319. https:\/\/doi.org\/10.1172\/JCI111390.","journal-title":"J Clin Invest"},{"key":"970_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2025.07.002","author":"A Correia-Rodrigues","year":"2025","unstructured":"Correia-Rodrigues A, Ribeiro-Rodrigues T, Goncalves L, Almeida JP, Ferreira MJ, Girao H. From pathophysiology to treatment in transthyretin cardiac amyloidosis. Trends Mol Med. 2025. https:\/\/doi.org\/10.1016\/j.molmed.2025.07.002.","journal-title":"Trends Mol Med"},{"issue":"1","key":"970_CR3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40246-024-00596-7","volume":"18","author":"A De Lillo","year":"2024","unstructured":"De Lillo A, Pathak GA, Low A, De Angelis F, Abou Alaiwi S, Miller EJ, Fuciarelli M, Polimanti R. Clinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins. Hum Genomics. 2024;18(1):31. https:\/\/doi.org\/10.1186\/s40246-024-00596-7.","journal-title":"Hum Genomics"},{"issue":"1","key":"970_CR4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1001\/jamacardio.2023.4147","volume":"9","author":"SJ Shah","year":"2024","unstructured":"Shah SJ, Fine N, Garcia-Pavia P, Klein AL, Fernandes F, Weissman NJ, Maurer MS, Boman K, Gundapaneni B, Sultan MB, et al. Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. JAMA Cardiol. 2024;9(1):25\u201334. https:\/\/doi.org\/10.1001\/jamacardio.2023.4147.","journal-title":"JAMA Cardiol"},{"issue":"7","key":"970_CR5","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1073\/pnas.87.7.2843","volume":"87","author":"P Westermark","year":"1990","unstructured":"Westermark P, Sletten K, Johansson B, Cornwell GG. 3rd: Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc Natl Acad Sci U S A. 1990;87(7):2843\u20135. https:\/\/doi.org\/10.1073\/pnas.87.7.2843.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"970_CR6","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1159\/000154146","volume":"43","author":"A Sousa","year":"1993","unstructured":"Sousa A, Andersson R, Drugge U, Holmgren G, Sandgren O. Familial amyloidotic polyneuropathy in Sweden: geographical distribution, age of onset, and prevalence. Hum Hered. 1993;43(5):288\u201394. https:\/\/doi.org\/10.1159\/000154146.","journal-title":"Hum Hered"},{"issue":"5","key":"970_CR7","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1136\/jmg.31.5.351","volume":"31","author":"G Holmgren","year":"1994","unstructured":"Holmgren G, Costa PM, Andersson C, Asplund K, Steen L, Beckman L, Nylander PO, Teixeira A, Saraiva MJ, Costa PP. Geographical distribution of TTR met30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate. J Med Genet. 1994;31(5):351\u20134. https:\/\/doi.org\/10.1136\/jmg.31.5.351.","journal-title":"J Med Genet"},{"issue":"Pt 4","key":"970_CR8","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/j.1469-1809.2008.00439.x","volume":"72","author":"C Zaros","year":"2008","unstructured":"Zaros C, Genin E, Hellman U, Saporta MA, Languille L, Wadington-Cruz M, Suhr O, Misrahi M, Plante-Bordeneuve V. On the origin of the transthyretin Val30Met familial amyloid polyneuropathy. Ann Hum Genet. 2008;72(Pt 4):478\u201384. https:\/\/doi.org\/10.1111\/j.1469-1809.2008.00439.x.","journal-title":"Ann Hum Genet"},{"issue":"4","key":"970_CR9","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1007\/s00415-017-8708-4","volume":"265","author":"V Plante-Bordeneuve","year":"2018","unstructured":"Plante-Bordeneuve V. Transthyretin familial amyloid polyneuropathy: an update. J Neurol. 2018;265(4):976\u201383. https:\/\/doi.org\/10.1007\/s00415-017-8708-4.","journal-title":"J Neurol"},{"issue":"2","key":"970_CR10","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1136\/jnnp-2011-301299","volume":"83","author":"H Koike","year":"2012","unstructured":"Koike H, Tanaka F, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, Fujitake J, Kawanami T, Kato T, Yamamoto M, et al. Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas. J Neurol Neurosurg Psychiatry. 2012;83(2):152\u20138. https:\/\/doi.org\/10.1136\/jnnp-2011-301299.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"8","key":"970_CR11","doi-asserted-by":"publisher","first-page":"101086","DOI":"10.1016\/j.jacadv.2024.101086","volume":"3","author":"N Mora-Ayestaran","year":"2024","unstructured":"Mora-Ayestaran N, Dispenzieri A, Kristen AV, Maurer MS, Diemberger I, Drachman BM, Grogan M, Gupta P, Glass O, Amass L, et al. Age- and Sex-Related Differences in Patients With Wild-Type Transthyretin Amyloidosis: Insights From THAOS. JACC Adv. 2024;3(8):101086. https:\/\/doi.org\/10.1016\/j.jacadv.2024.101086.","journal-title":"JACC Adv"},{"issue":"3","key":"970_CR12","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s40119-022-00265-7","volume":"11","author":"CM Campbell","year":"2022","unstructured":"Campbell CM, LoRusso S, Dispenzieri A, Kristen AV, Maurer MS, Rapezzi C, Lairez O, Drachman B, Garcia-Pavia P, Grogan M, et al. Sex Differences in Wild-Type Transthyretin Amyloidosis: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Cardiol Ther. 2022;11(3):393\u2013405. https:\/\/doi.org\/10.1007\/s40119-022-00265-7.","journal-title":"Cardiol Ther"},{"issue":"10","key":"970_CR13","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.jchf.2021.05.005","volume":"9","author":"AG Caponetti","year":"2021","unstructured":"Caponetti AG, Rapezzi C, Gagliardi C, Milandri A, Dispenzieri A, Kristen AV, Wixner J, Maurer MS, Garcia-Pavia P, Tournev I, et al. Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis: Insights From THAOS. JACC Heart Fail. 2021;9(10):736\u201346. https:\/\/doi.org\/10.1016\/j.jchf.2021.05.005.","journal-title":"JACC Heart Fail"},{"key":"970_CR14","doi-asserted-by":"publisher","unstructured":"Dominguez-Martinez M, Caro-Llopis A, Martin-Grau C, Rosello M, Oltra S, Pedrola L, Monfort S, Gabaldon-Albero A, Martinez F, Orellana C. Genetic landscape of hereditary transthyretin amyloidosis in Spain: a multicentric retrospective study. Amyloid 2025:1\u201311 https:\/\/doi.org\/10.1080\/13506129.2025.2527830","DOI":"10.1080\/13506129.2025.2527830"},{"issue":"13","key":"970_CR15","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.1016\/S0021-9258(19)43720-4","volume":"248","author":"PP van Jaarsveld","year":"1973","unstructured":"van Jaarsveld PP, Edelhoch H, Goodman DS, Robbins J. The interaction of human plasma retinol-binding protein and prealbumin. J Biol Chem. 1973;248(13):4698\u2013705.","journal-title":"J Biol Chem"},{"issue":"12","key":"970_CR16","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1016\/S0021-9258(18)93118-2","volume":"244","author":"A Raz","year":"1969","unstructured":"Raz A, Goodman DS. The interaction of thyroxine with human plasma prealbumin and with the prealbumin-retinol-binding protein complex. J Biol Chem. 1969;244(12):3230\u20137.","journal-title":"J Biol Chem"},{"issue":"36","key":"970_CR17","doi-asserted-by":"publisher","first-page":"8654","DOI":"10.1021\/bi00151a036","volume":"31","author":"W Colon","year":"1992","unstructured":"Colon W, Kelly JW. Partial denaturation of transthyretin is sufficient for amyloid fibril formation in vitro. Biochemistry. 1992;31(36):8654\u201360. https:\/\/doi.org\/10.1021\/bi00151a036.","journal-title":"Biochemistry"},{"issue":"41","key":"970_CR18","doi-asserted-by":"publisher","first-page":"13527","DOI":"10.1021\/bi00041a032","volume":"34","author":"SL McCutchen","year":"1995","unstructured":"McCutchen SL, Lai Z, Miroy GJ, Kelly JW, Colon W. Comparison of lethal and nonlethal transthyretin variants and their relationship to amyloid disease. Biochemistry. 1995;34(41):13527\u201336. https:\/\/doi.org\/10.1021\/bi00041a032.","journal-title":"Biochemistry"},{"key":"970_CR19","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/s0065-3233(08)60321-6","volume":"50","author":"JW Kelly","year":"1997","unstructured":"Kelly JW, Colon W, Lai Z, Lashuel HA, McCulloch J, McCutchen SL, Miroy GJ, Peterson SA. Transthyretin quaternary and tertiary structural changes facilitate misassembly into amyloid. Adv Protein Chem. 1997;50:161\u201381. https:\/\/doi.org\/10.1016\/s0065-3233(08)60321-6.","journal-title":"Adv Protein Chem"},{"issue":"5","key":"970_CR20","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1111\/j.1365-2796.2004.01399.x","volume":"256","author":"G Holmgren","year":"2004","unstructured":"Holmgren G, Wikstrom L, Lundgren HE, Suhr OB. Discordant penetrance of the trait for familial amyloidotic polyneuropathy in two pairs of monozygotic twins. J Intern Med. 2004;256(5):453\u20136. https:\/\/doi.org\/10.1111\/j.1365-2796.2004.01399.x.","journal-title":"J Intern Med"},{"key":"970_CR21","doi-asserted-by":"publisher","unstructured":"Jiang X, Labaudiniere R, Buxbaum JN, Monteiro C, Novais M, Coelho T, Kelly JW. A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction. Proc Natl Acad Sci U S A. 2021;118(9). https:\/\/doi.org\/10.1073\/pnas.2016072118.","DOI":"10.1073\/pnas.2016072118"},{"issue":"1","key":"970_CR22","doi-asserted-by":"publisher","first-page":"108031","DOI":"10.1016\/j.jbc.2024.108031","volume":"301","author":"SW Jayaweera","year":"2025","unstructured":"Jayaweera SW, Sahin M, Lundkvist F, Leven A, Tereenstra L, Backman J, Bachhar A, Bano F, Anan I, Olofsson A. Misfolding of transthyretin in vivo is controlled by the redox environment and macromolecular crowding. J Biol Chem. 2025;301(1):108031. https:\/\/doi.org\/10.1016\/j.jbc.2024.108031.","journal-title":"J Biol Chem"},{"issue":"2","key":"970_CR23","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/j.1460-2075.1993.tb05708.x","volume":"12","author":"C Thylen","year":"1993","unstructured":"Thylen C, Wahlqvist J, Haettner E, Sandgren O, Holmgren G, Lundgren E. Modifications of transthyretin in amyloid fibrils: analysis of amyloid from homozygous and heterozygous individuals with the Met30 mutation. EMBO J. 1993;12(2):743\u20138. https:\/\/doi.org\/10.1002\/j.1460-2075.1993.tb05708.x.","journal-title":"EMBO J"},{"issue":"1","key":"970_CR24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/s0002-9440(10)63123-9","volume":"164","author":"Y Takaoka","year":"2004","unstructured":"Takaoka Y, Ohta M, Miyakawa K, Nakamura O, Suzuki M, Takahashi K, Yamamura K, Sakaki Y. Cysteine 10 is a key residue in amyloidogenesis of human transthyretin Val30Met. Am J Pathol. 2004;164(1):337\u201345. https:\/\/doi.org\/10.1016\/s0002-9440(10)63123-9.","journal-title":"Am J Pathol"},{"issue":"Pt 2","key":"970_CR25","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1113\/jphysiol.2003.049478","volume":"552","author":"JF Turrens","year":"2003","unstructured":"Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335\u201344. https:\/\/doi.org\/10.1113\/jphysiol.2003.049478.","journal-title":"J Physiol"},{"key":"970_CR26","doi-asserted-by":"publisher","first-page":"105837","DOI":"10.1016\/j.neuint.2024.105837","volume":"179","author":"FN Eze","year":"2024","unstructured":"Eze FN. Transthyretin Amyloidosis: Role of oxidative stress and the beneficial implications of antioxidants and nutraceutical supplementation. Neurochem Int. 2024;179:105837. https:\/\/doi.org\/10.1016\/j.neuint.2024.105837.","journal-title":"Neurochem Int"},{"issue":"4","key":"970_CR27","doi-asserted-by":"publisher","first-page":"325","DOI":"10.5607\/en.2015.24.4.325","volume":"24","author":"GH Kim","year":"2015","unstructured":"Kim GH, Kim JE, Rhie SJ, Yoon S. The Role of Oxidative Stress in Neurodegenerative Diseases. Exp Neurobiol. 2015;24(4):325\u201340. https:\/\/doi.org\/10.5607\/en.2015.24.4.325.","journal-title":"Exp Neurobiol"},{"issue":"5","key":"970_CR28","doi-asserted-by":"publisher","first-page":"523","DOI":"10.2307\/3579270","volume":"145","author":"P Wardman","year":"1996","unstructured":"Wardman P, Candeias LP. Fenton chemistry: an introduction. Radiat Res. 1996;145(5):523\u201331.","journal-title":"Radiat Res"},{"issue":"3","key":"970_CR29","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/s0008-6363(99)00115-7","volume":"43","author":"PJ Andrew","year":"1999","unstructured":"Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999;43(3):521\u201331. https:\/\/doi.org\/10.1016\/s0008-6363(99)00115-7.","journal-title":"Cardiovasc Res"},{"issue":"12","key":"970_CR30","doi-asserted-by":"publisher","first-page":"24438","DOI":"10.3390\/ijms141224438","volume":"14","author":"J Li","year":"2013","unstructured":"Li J, O W, Li W, Jiang ZG, Ghanbari HA. Oxidative stress and neurodegenerative disorders. Int J Mol Sci. 2013;14(12):24438\u201375. https:\/\/doi.org\/10.3390\/ijms141224438.","journal-title":"Int J Mol Sci"},{"issue":"Suppl 2","key":"970_CR31","doi-asserted-by":"publisher","first-page":"S357","DOI":"10.3233\/JAD-2010-100498","volume":"20","author":"DA Patten","year":"2010","unstructured":"Patten DA, Germain M, Kelly MA, Slack RS. Reactive oxygen species: stuck in the middle of neurodegeneration. J Alzheimers Dis. 2010;20(Suppl 2):S357\u2013367. https:\/\/doi.org\/10.3233\/JAD-2010-100498.","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"970_CR32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1080\/13510002.2022.2046423","volume":"27","author":"B Zhang","year":"2022","unstructured":"Zhang B, Pan C, Feng C, Yan C, Yu Y, Chen Z, Guo C, Wang X. Role of mitochondrial reactive oxygen species in homeostasis regulation. Redox Rep. 2022;27(1):45\u201352. https:\/\/doi.org\/10.1080\/13510002.2022.2046423.","journal-title":"Redox Rep"},{"issue":"1","key":"970_CR33","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","volume":"8","author":"X Li","year":"2023","unstructured":"Li X, Li C, Zhang W, Wang Y, Qian P, Huang H. Inflammation and aging: signaling pathways and intervention therapies. Signal Transduct Target Ther. 2023;8(1):239. https:\/\/doi.org\/10.1038\/s41392-023-01502-8.","journal-title":"Signal Transduct Target Ther"},{"key":"970_CR34","doi-asserted-by":"publisher","unstructured":"Nakano T, Onoue K, Terada C, Terasaki S, Ishihara S, Hashimoto Y, Nakada Y, Nakagawa H, Ueda T, Seno A, et al. Transthyretin amyloid cardiomyopathy: impact of transthyretin amyloid deposition in myocardium on cardiac morphology and function. J Pers Med. 2022;12(5). https:\/\/doi.org\/10.3390\/jpm12050792.","DOI":"10.3390\/jpm12050792"},{"issue":"2","key":"970_CR35","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1006\/bbrc.1996.5997","volume":"232","author":"Y Ando","year":"1997","unstructured":"Ando Y, Nyhlin N, Suhr O, Holmgren G, Uchida K, el Sahly M, Yamashita T, Terasaki H, Nakamura M, Uchino M, et al. Oxidative stress is found in amyloid deposits in systemic amyloidosis. Biochem Biophys Res Commun. 1997;232(2):497\u2013502. https:\/\/doi.org\/10.1006\/bbrc.1996.5997.","journal-title":"Biochem Biophys Res Commun"},{"key":"970_CR36","doi-asserted-by":"publisher","first-page":"26623","DOI":"10.1038\/srep26623","volume":"6","author":"N Ferreira","year":"2016","unstructured":"Ferreira N, Goncalves NP, Saraiva MJ, Almeida MR. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis. Sci Rep. 2016;6:26623. https:\/\/doi.org\/10.1038\/srep26623.","journal-title":"Sci Rep"},{"issue":"6","key":"970_CR37","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.phrs.2010.08.001","volume":"62","author":"B Macedo","year":"2010","unstructured":"Macedo B, Magalhaes J, Batista AR, Saraiva MJ. Carvedilol treatment reduces transthyretin deposition in a familial amyloidotic polyneuropathy mouse model. Pharmacol Res. 2010;62(6):514\u201322. https:\/\/doi.org\/10.1016\/j.phrs.2010.08.001.","journal-title":"Pharmacol Res"},{"issue":"5","key":"970_CR38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nri3423","volume":"13","author":"C Nathan","year":"2013","unstructured":"Nathan C, Cunningham-Bussel A. Beyond oxidative stress: an immunologist\u2019s guide to reactive oxygen species. Nat Rev Immunol. 2013;13(5):349\u201361. https:\/\/doi.org\/10.1038\/nri3423.","journal-title":"Nat Rev Immunol"},{"key":"970_CR39","doi-asserted-by":"publisher","first-page":"1147414","DOI":"10.3389\/fphar.2023.1147414","volume":"14","author":"J Pei","year":"2023","unstructured":"Pei J, Pan X, Wei G, Hua Y. Research progress of glutathione peroxidase family (GPX) in redoxidation. Front Pharmacol. 2023;14:1147414. https:\/\/doi.org\/10.3389\/fphar.2023.1147414.","journal-title":"Front Pharmacol"},{"key":"970_CR40","doi-asserted-by":"publisher","unstructured":"Chen TH, Wang HC, Chang CJ, Lee SY. Mitochondrial glutathione in cellular redox homeostasis and disease manifestation. Int J Mol Sci. 2024;25(2). https:\/\/doi.org\/10.3390\/ijms25021314.","DOI":"10.3390\/ijms25021314"},{"issue":"2","key":"970_CR41","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/1873-3468.14261","volume":"596","author":"M Muraoka","year":"2022","unstructured":"Muraoka M, Yoshida S, Ohno M, Matsuura H, Nagano K, Hirata Y, Arai M, Hirata K. Reactivity of gamma-glutamyl-cysteine with intracellular and extracellular glutathione metabolic enzymes. FEBS Lett. 2022;596(2):180\u20138. https:\/\/doi.org\/10.1002\/1873-3468.14261.","journal-title":"FEBS Lett"},{"issue":"3","key":"970_CR42","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1073\/pnas.67.3.1248","volume":"67","author":"M Orlowski","year":"1970","unstructured":"Orlowski M, Meister A. The gamma-glutamyl cycle: a possible transport system for amino acids. Proc Natl Acad Sci U S A. 1970;67(3):1248\u201355. https:\/\/doi.org\/10.1073\/pnas.67.3.1248.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"970_CR43","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.cca.2017.08.022","volume":"473","author":"S Qi","year":"2017","unstructured":"Qi S, Xu D, Li Q, Xie N, Xia J, Huo Q, Li P, Chen Q, Huang S. Metabonomics screening of serum identifies pyroglutamate as a diagnostic biomarker for nonalcoholic steatohepatitis. Clin Chim Acta. 2017;473:89\u201395. https:\/\/doi.org\/10.1016\/j.cca.2017.08.022.","journal-title":"Clin Chim Acta"},{"issue":"1","key":"970_CR44","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1186\/s13075-021-02681-x","volume":"23","author":"M Wang","year":"2021","unstructured":"Wang M, Chen J, Lin X, Huang L, Li H, Wen C, He Z. High humidity aggravates the severity of arthritis in collagen-induced arthritis mice by upregulating xylitol and L-pyroglutamic acid. Arthritis Res Ther. 2021;23(1):292. https:\/\/doi.org\/10.1186\/s13075-021-02681-x.","journal-title":"Arthritis Res Ther"},{"issue":"2","key":"970_CR45","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1093\/rheumatology\/keaa126","volume":"60","author":"Q Zhang","year":"2021","unstructured":"Zhang Q, Li X, Yin X, Wang H, Fu C, Wang H, Li K, Li Y, Zhang X, Liang H, et al. Metabolomic profiling reveals serum L-pyroglutamic acid as a potential diagnostic biomarker for systemic lupus erythematosus. Rheumatology (Oxford). 2021;60(2):598\u2013606. https:\/\/doi.org\/10.1093\/rheumatology\/keaa126.","journal-title":"Rheumatology (Oxford)"},{"issue":"4","key":"970_CR46","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1093\/gerona\/glab163","volume":"77","author":"PA Dugue","year":"2022","unstructured":"Dugue PA, Hodge AM, Ulvik A, Ueland PM, Midttun O, Rinaldi S, MacInnis RJ, Li SX, Meyer K, Navionis AS, et al. Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging. J Gerontol Biol Sci Med Sci. 2022;77(4):826\u201336. https:\/\/doi.org\/10.1093\/gerona\/glab163.","journal-title":"J Gerontol Biol Sci Med Sci"},{"issue":"1","key":"970_CR47","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12974-020-1721-z","volume":"17","author":"B Pedraz-Petrozzi","year":"2020","unstructured":"Pedraz-Petrozzi B, Elyamany O, Rummel C, Mulert C. Effects of inflammation on the kynurenine pathway in schizophrenia - a systematic review. J Neuroinflammation. 2020;17(1):56. https:\/\/doi.org\/10.1186\/s12974-020-1721-z.","journal-title":"J Neuroinflammation"},{"issue":"4","key":"970_CR48","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/aje\/kwv242","volume":"183","author":"H Zuo","year":"2016","unstructured":"Zuo H, Ueland PM, Ulvik A, Eussen SJ, Vollset SE, Nygard O, Midttun O, Theofylaktopoulou D, Meyer K, Tell GS. Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All-Cause, Cancer, and Cardiovascular Disease Mortality: The Hordaland Health Study. Am J Epidemiol. 2016;183(4):249\u201358. https:\/\/doi.org\/10.1093\/aje\/kwv242.","journal-title":"Am J Epidemiol"},{"key":"970_CR49","doi-asserted-by":"publisher","unstructured":"Tretter V, Hochreiter B, Zach ML, Krenn K, Klein KU. Understanding cellular redox homeostasis: a challenge for precision medicine. Int J Mol Sci. 2021;23(1). https:\/\/doi.org\/10.3390\/ijms23010106.","DOI":"10.3390\/ijms23010106"},{"issue":"4","key":"970_CR50","doi-asserted-by":"publisher","first-page":"193","DOI":"10.33696\/signaling.3.083","volume":"3","author":"A Yamamoto","year":"2022","unstructured":"Yamamoto A, Sly PD, Henningham A, Begum N, Yeo AJ, Fantino E. Redox Homeostasis in Well-differentiated Primary Human Nasal Epithelial Cells. J Cell Signal. 2022;3(4):193\u2013206. https:\/\/doi.org\/10.33696\/signaling.3.083.","journal-title":"J Cell Signal"},{"issue":"1","key":"970_CR51","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13023-020-01565-8","volume":"15","author":"H Paulsson Rokke","year":"2020","unstructured":"Paulsson Rokke H, Sadat Gousheh N, Westermark P, Suhr OB, Anan I, Ihse E, Pilebro B, Wixner J. Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspected transthyretin amyloidosis. Orphanet J Rare Dis. 2020;15(1):278. https:\/\/doi.org\/10.1186\/s13023-020-01565-8.","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"970_CR52","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3109\/13506129.2013.860027","volume":"21","author":"M Olsson","year":"2014","unstructured":"Olsson M, Jonasson J, Cederquist K, Suhr OB. Frequency of the transthyretin Val30Met mutation in the northern Swedish population. Amyloid. 2014;21(1):18\u201320. https:\/\/doi.org\/10.3109\/13506129.2013.860027.","journal-title":"Amyloid"},{"issue":"12","key":"970_CR53","doi-asserted-by":"publisher","first-page":"5633","DOI":"10.1021\/ac501451v","volume":"86","author":"P Purwaha","year":"2014","unstructured":"Purwaha P, Silva LP, Hawke DH, Weinstein JN, Lorenzi PL. An artifact in LC-MS\/MS measurement of glutamine and glutamic acid: in-source cyclization to pyroglutamic acid. Anal Chem. 2014;86(12):5633\u20137. https:\/\/doi.org\/10.1021\/ac501451v.","journal-title":"Anal Chem"},{"issue":"2","key":"970_CR54","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jneumeth.2008.02.019","volume":"171","author":"JA Eckstein","year":"2008","unstructured":"Eckstein JA, Ammerman GM, Reveles JM, Ackermann BL. Analysis of glutamine, glutamate, pyroglutamate, and GABA in cerebrospinal fluid using ion pairing HPLC with positive electrospray LC\/MS\/MS. J Neurosci Methods. 2008;171(2):190\u20136. https:\/\/doi.org\/10.1016\/j.jneumeth.2008.02.019.","journal-title":"J Neurosci Methods"},{"key":"970_CR55","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jchromb.2013.10.011","volume":"941","author":"J Wu","year":"2013","unstructured":"Wu J, Wiegand R, LoRusso P, Li J. A stable isotope-labeled internal standard is essential for correcting for the interindividual variability in the recovery of lapatinib from cancer patient plasma in quantitative LC-MS\/MS analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;941:100\u20138. https:\/\/doi.org\/10.1016\/j.jchromb.2013.10.011.","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"970_CR56","doi-asserted-by":"publisher","first-page":"123719","DOI":"10.1016\/j.jchromb.2023.123719","volume":"1222","author":"O Hodek","year":"2023","unstructured":"Hodek O, Henderson J, Argemi-Muntadas L, Khan A, Moritz T. Structural elucidation of 3-nitrophenylhydrazine derivatives of tricarboxylic acid cycle acids and optimization of their fragmentation to boost sensitivity in liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2023;1222:123719. https:\/\/doi.org\/10.1016\/j.jchromb.2023.123719.","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"issue":"29","key":"970_CR57","doi-asserted-by":"publisher","first-page":"10075","DOI":"10.1021\/acs.analchem.1c00767","volume":"93","author":"X Meng","year":"2021","unstructured":"Meng X, Pang H, Sun F, Jin X, Wang B, Yao K, Yao L, Wang L, Hu Z. Simultaneous 3-Nitrophenylhydrazine Derivatization Strategy of Carbonyl, Carboxyl and Phosphoryl Submetabolome for LC-MS\/MS-Based Targeted Metabolomics with Improved Sensitivity and Coverage. Anal Chem. 2021;93(29):10075\u201383. https:\/\/doi.org\/10.1021\/acs.analchem.1c00767.","journal-title":"Anal Chem"},{"issue":"11 Pt A","key":"970_CR58","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1016\/j.bbagen.2016.07.002","volume":"1860","author":"PB Larkin","year":"2016","unstructured":"Larkin PB, Sathyasaikumar KV, Notarangelo FM, Funakoshi H, Nakamura T, Schwarcz R, Muchowski PJ. Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice. Biochim Biophys Acta. 2016;1860(11 Pt A):2345\u201354. https:\/\/doi.org\/10.1016\/j.bbagen.2016.07.002.","journal-title":"Biochim Biophys Acta"},{"key":"970_CR59","doi-asserted-by":"publisher","first-page":"117864691769193","DOI":"10.1177\/1178646917691938","volume":"10","author":"AA Badawy","year":"2017","unstructured":"Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res. 2017;10:1178646917691938. https:\/\/doi.org\/10.1177\/1178646917691938.","journal-title":"Int J Tryptophan Res"},{"issue":"4","key":"970_CR60","doi-asserted-by":"publisher","first-page":"103019","DOI":"10.1016\/j.cpcardiol.2025.103019","volume":"50","author":"F Triposkiadis","year":"2025","unstructured":"Triposkiadis F, Briasoulis A, Starling RC, Magouliotis DE, Kourek C, Zakynthinos GE, Iliodromitis EK, Paraskevaidis I, Xanthopoulos A. Hereditary transthyretin amyloidosis (ATTRv). Curr Probl Cardiol. 2025;50(4):103019. https:\/\/doi.org\/10.1016\/j.cpcardiol.2025.103019.","journal-title":"Curr Probl Cardiol"},{"issue":"20","key":"970_CR61","doi-asserted-by":"publisher","first-page":"6099","DOI":"10.1111\/febs.16086","volume":"289","author":"MT Pallotta","year":"2022","unstructured":"Pallotta MT, Rossini S, Suvieri C, Coletti A, Orabona C, Macchiarulo A, Volpi C, Grohmann U. Indoleamine 2,3-dioxygenase 1 (IDO1): an up-to-date overview of an eclectic immunoregulatory enzyme. FEBS J. 2022;289(20):6099\u2013118. https:\/\/doi.org\/10.1111\/febs.16086.","journal-title":"FEBS J"},{"issue":"20","key":"970_CR62","doi-asserted-by":"publisher","first-page":"2598","DOI":"10.1080\/15384101.2019.1652471","volume":"18","author":"G Guo","year":"2019","unstructured":"Guo G, Sun L, Yang L, Xu H. IDO1 depletion induces an anti-inflammatory response in macrophages in mice with chronic viral myocarditis. Cell Cycle. 2019;18(20):2598\u2013613. https:\/\/doi.org\/10.1080\/15384101.2019.1652471.","journal-title":"Cell Cycle"},{"key":"970_CR63","doi-asserted-by":"publisher","first-page":"117864691986897","DOI":"10.1177\/1178646919868978","volume":"12","author":"AA Badawy","year":"2019","unstructured":"Badawy AA, Guillemin G. The Plasma [Kynurenine]\/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal. Int J Tryptophan Res. 2019;12:1178646919868978. https:\/\/doi.org\/10.1177\/1178646919868978.","journal-title":"Int J Tryptophan Res"},{"issue":"33","key":"970_CR64","doi-asserted-by":"publisher","first-page":"11122","DOI":"10.1021\/bi050327i","volume":"44","author":"S Saito","year":"2005","unstructured":"Saito S, Ando Y, Nakamura M, Ueda M, Kim J, Ishima Y, Akaike T, Otagiri M. Effect of nitric oxide in amyloid fibril formation on transthyretin-related amyloidosis. Biochemistry. 2005;44(33):11122\u20139. https:\/\/doi.org\/10.1021\/bi050327i.","journal-title":"Biochemistry"},{"issue":"1","key":"970_CR65","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s13054-019-2450-5","volume":"23","author":"Y Gamarra","year":"2019","unstructured":"Gamarra Y, Santiago FC, Molina-Lopez J, Castano J, Herrera-Quintana L, Dominguez A, Planells E. Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock. Crit Care. 2019;23(1):162. https:\/\/doi.org\/10.1186\/s13054-019-2450-5.","journal-title":"Crit Care"},{"key":"970_CR66","doi-asserted-by":"publisher","unstructured":"Li M, Zhang R, Xin M, Xu Y, Liu S, Yu B, Zhang B, Liu J. Discovery and Validation of potential serum biomarkers with pro-inflammatory and DNA damage activities in ulcerative colitis: a comprehensive untargeted metabolomic study. Metabolites. 2022;12(10). https:\/\/doi.org\/10.3390\/metabo12100997.","DOI":"10.3390\/metabo12100997"},{"issue":"8","key":"970_CR67","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1097\/FPC.0000000000000150","volume":"25","author":"LL Mazaleuskaya","year":"2015","unstructured":"Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015;25(8):416\u201326. https:\/\/doi.org\/10.1097\/FPC.0000000000000150.","journal-title":"Pharmacogenet Genomics"},{"issue":"4","key":"970_CR68","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.amjms.2017.08.001","volume":"355","author":"HM Alhourani","year":"2018","unstructured":"Alhourani HM, Kumar A, George LK, Sarwar T, Wall BM. Recurrent Pyroglutamic Acidosis Related to Therapeutic Acetaminophen. Am J Med Sci. 2018;355(4):387\u20139. https:\/\/doi.org\/10.1016\/j.amjms.2017.08.001.","journal-title":"Am J Med Sci"},{"issue":"2","key":"970_CR69","doi-asserted-by":"publisher","first-page":"100030","DOI":"10.1016\/j.clinme.2024.100030","volume":"24","author":"GW Stewart","year":"2024","unstructured":"Stewart GW. Pyroglutamate acidosis 2023. A review of 100 cases. Clin Med (Lond). 2024;24(2):100030. https:\/\/doi.org\/10.1016\/j.clinme.2024.100030.","journal-title":"Clin Med (Lond)"},{"issue":"12","key":"970_CR70","doi-asserted-by":"publisher","first-page":"3606","DOI":"10.1093\/jn\/nxab309","volume":"151","author":"RV Sekhar","year":"2021","unstructured":"Sekhar RV. GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging. J Nutr. 2021;151(12):3606\u201316. https:\/\/doi.org\/10.1093\/jn\/nxab309.","journal-title":"J Nutr"},{"issue":"1","key":"970_CR71","first-page":"81","volume":"18","author":"MF McCarty","year":"2018","unstructured":"McCarty MF, O\u2019Keefe JH, DiNicolantonio JJ. Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. Ochsner J. 2018;18(1):81\u20137.","journal-title":"Ochsner J"},{"key":"970_CR72","doi-asserted-by":"publisher","first-page":"9584932","DOI":"10.1155\/2017\/9584932","volume":"2017","author":"P Bin","year":"2017","unstructured":"Bin P, Huang R, Zhou X. Oxidation Resistance of the Sulfur Amino Acids: Methionine and Cysteine. Biomed Res Int. 2017;2017:9584932. https:\/\/doi.org\/10.1155\/2017\/9584932.","journal-title":"Biomed Res Int"},{"issue":"10","key":"970_CR73","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.braindev.2015.03.005","volume":"37","author":"X Li","year":"2015","unstructured":"Li X, Ding Y, Liu Y, Ma Y, Song J, Wang Q, Yang Y. Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies. Brain Dev. 2015;37(10):952\u20139. https:\/\/doi.org\/10.1016\/j.braindev.2015.03.005.","journal-title":"Brain Dev"},{"key":"970_CR74","doi-asserted-by":"publisher","first-page":"1212405","DOI":"10.3389\/fped.2023.1212405","volume":"11","author":"X Wu","year":"2023","unstructured":"Wu X, Jiao J, Xia Y, Yan X, Liu Z, Cao Y, Ma L. Case report: A Chinese patient with glutathione synthetase deficiency and a novel glutathione synthase mutation. Front Pediatr. 2023;11:1212405. https:\/\/doi.org\/10.3389\/fped.2023.1212405.","journal-title":"Front Pediatr"},{"issue":"6","key":"970_CR75","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1073\/pnas.71.6.2505","volume":"71","author":"VP Wellner","year":"1974","unstructured":"Wellner VP, Sekura R, Meister A, Larsson A. Glutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria). Proc Natl Acad Sci U S A. 1974;71(6):2505\u20139. https:\/\/doi.org\/10.1073\/pnas.71.6.2505.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"970_CR76","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12883-019-1369-4","volume":"19","author":"EP Azevedo","year":"2019","unstructured":"Azevedo EP, Guimaraes-Costa AB, Bandeira-Melo C, Chimelli L, Waddington-Cruz M, Saraiva EM, Palhano FL, Foguel D. Inflammatory profiling of patients with familial amyloid polyneuropathy. BMC Neurol. 2019;19(1):146. https:\/\/doi.org\/10.1186\/s12883-019-1369-4.","journal-title":"BMC Neurol"},{"key":"970_CR77","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.bbrc.2022.12.027","volume":"642","author":"C Magaud","year":"2023","unstructured":"Magaud C, Harnois T, Sebille S, Chatelier A, Faivre JF, Bois P, Page G, Gellen B. Pro-inflammatory cytokine secretion induced by amyloid transthyretin in human cardiac fibroblasts. Biochem Biophys Res Commun. 2023;642:83\u20139. https:\/\/doi.org\/10.1016\/j.bbrc.2022.12.027.","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"970_CR78","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/cei.12092","volume":"173","author":"D Theofylaktopoulou","year":"2013","unstructured":"Theofylaktopoulou D, Midttun O, Ulvik A, Ueland PM, Tell GS, Vollset SE, Nygard O, Eussen SJ. A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study. Clin Exp Immunol. 2013;173(1):121\u201330. https:\/\/doi.org\/10.1111\/cei.12092.","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"970_CR79","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/s10067-005-0056-6","volume":"25","author":"K Schroecksnadel","year":"2006","unstructured":"Schroecksnadel K, Winkler C, Duftner C, Wirleitner B, Schirmer M, Fuchs D. Tryptophan degradation increases with stage in patients with rheumatoid arthritis. Clin Rheumatol. 2006;25(3):334\u20137. https:\/\/doi.org\/10.1007\/s10067-005-0056-6.","journal-title":"Clin Rheumatol"},{"issue":"10","key":"970_CR80","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1007\/s10067-022-06263-3","volume":"41","author":"D Wu","year":"2022","unstructured":"Wu D, Chen M, Chen S, Zhang S, Chen Y, Zhao Q, Xue K, Xue F, Chen X, Zhou M, et al. Enhanced tryptophan-kynurenine metabolism via indoleamine 2,3-dioxygenase 1 induction in dermatomyositis. Clin Rheumatol. 2022;41(10):3107\u201317. https:\/\/doi.org\/10.1007\/s10067-022-06263-3.","journal-title":"Clin Rheumatol"},{"issue":"7","key":"970_CR81","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1007\/s00018-019-03357-1","volume":"77","author":"RB Ibrahim","year":"2020","unstructured":"Ibrahim RB, Yeh SY, Lin KP, Ricardo F, Yu TY, Chan CC, Tsai JW, Liu YT. Cellular secretion and cytotoxicity of transthyretin mutant proteins underlie late-onset amyloidosis and neurodegeneration. Cell Mol Life Sci. 2020;77(7):1421\u201334. https:\/\/doi.org\/10.1007\/s00018-019-03357-1.","journal-title":"Cell Mol Life Sci"},{"issue":"2","key":"970_CR82","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3109\/13506129.2015.1007497","volume":"22","author":"L Moreira","year":"2015","unstructured":"Moreira L, Beirao JM, Beirao I, Pinho e Costa P. Oligomeric TTR V30M aggregates compromise cell viability, erythropoietin gene expression and promoter activity in the human hepatoma cell line Hep3B. Amyloid. 2015;22(2):93\u20139. https:\/\/doi.org\/10.3109\/13506129.2015.1007497.","journal-title":"Amyloid"},{"issue":"4","key":"970_CR83","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.bbrc.2011.04.133","volume":"410","author":"S Bourgault","year":"2011","unstructured":"Bourgault S, Choi S, Buxbaum JN, Kelly JW, Price JL, Reixach N. Mechanisms of transthyretin cardiomyocyte toxicity inhibition by resveratrol analogs. Biochem Biophys Res Commun. 2011;410(4):707\u201313. https:\/\/doi.org\/10.1016\/j.bbrc.2011.04.133.","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"970_CR84","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1080\/13506120802524916","volume":"15","author":"M Lindhagen-Persson","year":"2008","unstructured":"Lindhagen-Persson M, Vestling M, Reixach N, Olofsson A. Formation of cytotoxic transthyretin is not dependent on inter-molecular disulphide bridges commonly found within the amyloid form. Amyloid. 2008;15(4):240\u20135. https:\/\/doi.org\/10.1080\/13506120802524916.","journal-title":"Amyloid"},{"issue":"9","key":"970_CR85","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1073\/pnas.0400062101","volume":"101","author":"N Reixach","year":"2004","unstructured":"Reixach N, Deechongkit S, Jiang X, Kelly JW, Buxbaum JN. Tissue damage in the amyloidoses: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci U S A. 2004;101(9):2817\u201322. https:\/\/doi.org\/10.1073\/pnas.0400062101.","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Biomarker Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40364-026-00970-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-026-00970-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-026-00970-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:42:21Z","timestamp":1783953741000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40364-026-00970-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["970"],"URL":"https:\/\/doi.org\/10.1186\/s40364-026-00970-8","relation":{},"ISSN":["2050-7771"],"issn-type":[{"value":"2050-7771","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]},"assertion":[{"value":"25 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"These results were presented in parts at the Metabolomics in Life Science conference, 27\u201328 January 2026, Ume\u00e5, Sweden.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors note"}},{"value":"The authors acknowledge the use of Microsoft Copilot AI to generate the eukaryotic cell image and the image of a human body used as a component in Fig.\u00a0\n                      \n                      .","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Use of artificial intelligence"}},{"value":",\n                      \n                      ,","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Links"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"83"}}