{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:19:26Z","timestamp":1783408766898,"version":"3.54.6"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metab Brain Dis"],"DOI":"10.1007\/s11011-026-01907-8","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:58:49Z","timestamp":1783407529000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transthyretin at the crossroads of neurodegeneration: a silent guardian in Parkinson\u2019s disease"],"prefix":"10.1007","volume":"41","author":[{"given":"Priti","family":"Dipa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2450-2975","authenticated-orcid":false,"given":"Khadga Raj","family":"Aran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"1907_CR46","doi-asserted-by":"crossref","unstructured":"Adams D, Koike H, Slama M, Coelho T (2019) Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol 15(7):387\u2013404","DOI":"10.1038\/s41582-019-0210-4"},{"issue":"1","key":"1907_CR1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1159\/000548021","volume":"32","author":"KM Alem\u00e1n-Villa","year":"2025","unstructured":"Alem\u00e1n-Villa KM, Armienta-Rojas DA, Camberos-Barraza J, R\u00e1bago-Monz\u00f3n \u00c1R, Camacho-Zamora A, Osuna-Ramos JF, Maga\u00f1a-G\u00f3mez JA, Guadr\u00f3n-Llanos AM, Calder\u00f3n-Zamora L, Norzagaray-Valenzuela CD, Valdez-Flores MA (2025) Neuroinflammation across the spectrum of neurodegenerative diseases: mechanisms and therapeutic frontiers. Neuroimmunomodulation 32(1):278\u2013305. https:\/\/doi.org\/10.1159\/000548021","journal-title":"Neuroimmunomodulation"},{"issue":"5","key":"1907_CR3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/jne.12271","volume":"27","author":"B Alshehri","year":"2015","unstructured":"Alshehri B, D\u2019Souza DG, Lee JY, Petratos S, Richardson SJ (2015) The diversity of mechanisms influenced by transthyretin in neurobiology: development, disease and endocrine disruption. J Neuroendocrinol 27(5):303\u2013323. https:\/\/doi.org\/10.1111\/jne.12271","journal-title":"J Neuroendocrinol"},{"issue":"3","key":"1907_CR5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.neuint.2010.05.014","volume":"57","author":"S Arg\u00fcelles","year":"2010","unstructured":"Arg\u00fcelles S, Venero JL, Garc\u00eda-Rodriguez S, Tomas-Camardiel M, Ayala A, Cano J, Machado A (2010) Use of haptoglobin and transthyretin as potential biomarkers for the preclinical diagnosis of Parkinson\u2019s disease. Neurochem Int 57(3):227\u2013234. https:\/\/doi.org\/10.1016\/j.neuint.2010.05.014","journal-title":"Neurochem Int"},{"issue":"9","key":"1907_CR2","doi-asserted-by":"publisher","first-page":"e789","DOI":"10.1038\/cddis.2013.325","volume":"4","author":"EP Azevedo","year":"2013","unstructured":"Azevedo EP, Ledo JH, Barbosa G, Sobrinho M, Diniz L, Fonseca AC, Gomes F, Romao L, Lima FR, Palhano FL, Ferreira ST (2013) Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis. Cell Death Dis 4(9):e789. https:\/\/doi.org\/10.1038\/cddis.2013.325","journal-title":"Cell Death Dis"},{"key":"1907_CR6","doi-asserted-by":"publisher","first-page":"592644","DOI":"10.3389\/fnmol.2020.592644","volume":"13","author":"F Bezerra","year":"2020","unstructured":"Bezerra F, Saraiva MJ, Almeida MR (2020) Modulation of the mechanisms driving transthyretin amyloidosis. Front Mol Neurosci 13:592644. https:\/\/doi.org\/10.3389\/fnmol.2020.592644","journal-title":"Front Mol Neurosci"},{"key":"1907_CR7","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/jnc.13731","volume":"139","author":"A Bose","year":"2016","unstructured":"Bose A, Beal MF (2016) Mitochondrial dysfunction in Parkinson\u2019s disease. J Neurochem 139:216\u2013231. https:\/\/doi.org\/10.1111\/jnc.13731","journal-title":"J Neurochem"},{"issue":"3","key":"1907_CR9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41419-023-05672-9","volume":"14","author":"P Calabresi","year":"2023","unstructured":"Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V (2023) Alpha-synuclein in Parkinson\u2019s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis 14(3):176. https:\/\/doi.org\/10.1038\/s41419-023-05672-9","journal-title":"Cell Death Dis"},{"key":"1907_CR10","doi-asserted-by":"publisher","unstructured":"Cardoso I, Santos LM, Alemi M (2016) Modulating role of TTR in A\u03b2 toxicity, from health to disease. InExploring New Findings on Amyloidosis. Aug 24. IntechOpen. https:\/\/doi.org\/10.5772\/63194","DOI":"10.5772\/63194"},{"key":"1907_CR11","doi-asserted-by":"publisher","unstructured":"Chaudhary R, Rehman M, Agarwal V, Kaushik AS, Mishra V Protein aggregation in neurodegenerative diseases. InNeurodegenerative Diseases: Multifactorial Degenerative Processes, Biomarkers and Therapeutic Approaches 2022 Aug 9 (pp. 26\u201358). Bentham Science. https:\/\/doi.org\/10.2174\/97898150409131220101","DOI":"10.2174\/97898150409131220101"},{"issue":"3","key":"1907_CR13","doi-asserted-by":"publisher","first-page":"2945","DOI":"10.1007\/s12035-024-04442-8","volume":"62","author":"C Corino","year":"2025","unstructured":"Corino C, Aimo A, Luigetti M, Ciccone L, Ferrari Chen YF, Panichella G, Musetti V, Castiglione V, Vergaro G, Emdin M, Franzini M (2025) Tetrameric transthyretin as a protective factor against Alzheimer\u2019s disease. Mol Neurobiol 62(3):2945\u20132954. https:\/\/doi.org\/10.1007\/s12035-024-04442-8","journal-title":"Mol Neurobiol"},{"issue":"8","key":"1907_CR69","doi-asserted-by":"publisher","first-page":"e2899","DOI":"10.1371\/journal.pone.0002899","volume":"3","author":"R Costa","year":"2008","unstructured":"Costa R, Ferreira-da-Silva F, Saraiva MJ, Cardoso I (2008) Transthyretin protects against A-beta peptide toxicity by proteolytic cleavage of the peptide: a mechanism sensitive to the Kunitz protease inhibitor. PLoS ONE 3(8):e2899. https:\/\/doi.org\/10.1371\/journal.pone.0002899","journal-title":"PLoS ONE"},{"issue":"7","key":"1907_CR14","doi-asserted-by":"publisher","first-page":"e0125392","DOI":"10.1371\/journal.pone.0125392","volume":"10","author":"G Da Costa","year":"2015","unstructured":"Da Costa G, Ribeiro-Silva C, Ribeiro R, Gilberto S, Gomes RA, Ferreira A, Mateus E, Barroso E, Coelho AV, Freire AP, Cordeiro C (2015) Transthyretin amyloidosis: chaperone concentration changes and increased proteolysis in the pathway to disease. PLoS ONE 10(7):e0125392. https:\/\/doi.org\/10.1371\/journal.pone.0125392","journal-title":"PLoS ONE"},{"key":"1907_CR15","doi-asserted-by":"publisher","unstructured":"do Amaral Martins L, Ferreira PS, Dos Santos OA, Martins LO, Barroso LG, Pereira HM, Waddington-Cruz M, Palhano FL, Foguel D (2024) Structural and thermodynamic characterization of a highly amyloidogenic dimer of transthyretin involved in a severe cardiomyopathy. J Biol Chem 300(8). https:\/\/doi.org\/10.1016\/j.jbc.2024.107495","DOI":"10.1016\/j.jbc.2024.107495"},{"issue":"1","key":"1907_CR16","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s42466-021-00155-8","volume":"3","author":"MF Dohrn","year":"2021","unstructured":"Dohrn MF, Medina J, Olaciregui Dague KR, Hund E (2021) Are we creating a new phenotype? Physiological barriers and ethical considerations in the treatment of hereditary transthyretin-amyloidosis. Neurol Res Pract 3(1):57. https:\/\/doi.org\/10.1186\/s42466-021-00155-8","journal-title":"Neurol Res Pract"},{"key":"1907_CR17","doi-asserted-by":"publisher","unstructured":"Du\u00f1abeitia I, Gonz\u00e1lez-Devesa D, Blanco-Mart\u00ednez N, Ay\u00e1n-P\u00e9rez C (2025) The effects of stretching in Parkinson\u2019s disease: a systematic review of randomized controlled trials. Parkinsonism Relat Disord 107796. https:\/\/doi.org\/10.1016\/j.parkreldis.2025.107796","DOI":"10.1016\/j.parkreldis.2025.107796"},{"key":"1907_CR23","doi-asserted-by":"crossref","unstructured":"Eze FN (2024) Transthyretin amyloidosis: role of oxidative stress and the beneficial implications of antioxidants and nutraceutical supplementation. Neurochem Int 179:105837","DOI":"10.1016\/j.neuint.2024.105837"},{"issue":"1","key":"1907_CR18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/cpdd.700","volume":"9","author":"JC Fox","year":"2020","unstructured":"Fox JC, Hellawell JL, Rao S, O\u2019Reilly T, Lumpkin R, Jernelius J, Gretler D, Sinha U (2020) First-in\u2010human study of AG10, a novel, oral, specific, selective, and potent transthyretin stabilizer for the treatment of transthyretin amyloidosis: a phase 1 safety, tolerability, pharmacokinetic, and pharmacodynamic study in healthy adult volunteers. Clin Pharmacol Drug Dev 9(1):115\u2013129. https:\/\/doi.org\/10.1002\/cpdd.700","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"1","key":"1907_CR19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s13195-021-00883-8","volume":"13","author":"T Gi\u00e3o","year":"2021","unstructured":"Gi\u00e3o T, Saavedra J, Vieira JR, Pinto MT, Arsequell G, Cardoso I (2021) Neuroprotection in early stages of Alzheimer\u2019s disease is promoted by transthyretin angiogenic properties. Alzheimers Res Ther 13(1):143. https:\/\/doi.org\/10.1186\/s13195-021-00883-8","journal-title":"Alzheimers Res Ther"},{"issue":"11","key":"1907_CR72","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1038\/cdd.2016.64","volume":"23","author":"JR Gomes","year":"2016","unstructured":"Gomes JR, Nogueira RS, Vieira M, Santos SD, Ferraz-Nogueira JP, Relvas JB, Saraiva MJ (2016) Transthyretin provides trophic support via megalin by promoting neurite outgrowth and neuroprotection in cerebral ischemia. Cell Death Differ 23(11):1749\u20131764. https:\/\/doi.org\/10.1038\/cdd.2016.64","journal-title":"Cell Death Differ"},{"issue":"1","key":"1907_CR21","doi-asserted-by":"publisher","first-page":"117","DOI":"10.17996\/anc.22-00162","volume":"8","author":"F Haga","year":"2022","unstructured":"Haga F, Oikawa M, Akama J, Kiko T, Yamada S, Yoshihisa A, Nakazato K, Takeishi Y (2022) ATTR amyloidosis concomitant with parkinsonism and cardiac sympathetic neuropathy. Annals Nuclear Cardiol 8(1):117\u2013119. https:\/\/doi.org\/10.17996\/anc.22-00162","journal-title":"Annals Nuclear Cardiol"},{"issue":"1","key":"1907_CR22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13024-015-0059-y","volume":"10","author":"WE Heywood","year":"2015","unstructured":"Heywood WE, Galimberti D, Bliss E, Sirka E, Paterson RW, Magdalinou NK, Carecchio M, Reid E, Heslegrave A, Fenoglio C, Scarpini E (2015) Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay. Mol neurodegeneration 10(1):64. https:\/\/doi.org\/10.1186\/s13024-015-0059-y","journal-title":"Mol neurodegeneration"},{"key":"1907_CR4","doi-asserted-by":"publisher","unstructured":"Huang M, Bargues-Carot A, Riaz Z, Wickham H, Zenitsky G, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG (2022) Impact of environmental risk factors on mitochondrial dysfunction, neuroinflammation, protein misfolding, and oxidative stress in the etiopathogenesis of Parkinson\u2019s disease. Int J Mol Sci 23(18):10808. https:\/\/doi.org\/10.3390\/pharmaceutics13111779","DOI":"10.3390\/pharmaceutics13111779"},{"key":"1907_CR25","doi-asserted-by":"publisher","first-page":"115735","DOI":"10.1016\/j.biopha.2023.115735","volume":"168","author":"Q Huang","year":"2023","unstructured":"Huang Q, Yang P, Liu Y, Ding J, Lu M, Hu G (2023) The interplay between \u03b1-Synuclein and NLRP3 inflammasome in Parkinson\u2019s disease. Biomed Pharmacother 168:115735. https:\/\/doi.org\/10.1016\/j.biopha.2023.115735","journal-title":"Biomed Pharmacother"},{"issue":"33","key":"1907_CR28","doi-asserted-by":"publisher","first-page":"E7710","DOI":"10.1073\/pnas.1801117115","volume":"115","author":"X Jiang","year":"2018","unstructured":"Jiang X, Ooi FK, Lemos C (2018) Cellular clearance of circulating transthyretin decreases cell-nonautonomous proteotoxicity in Caenorhabditis elegans. Proceedings of the National Academy of Sciences 115(33): E7710-9. https:\/\/doi.org\/10.1073\/pnas.1801117115","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"19","key":"1907_CR29","doi-asserted-by":"publisher","first-page":"7113","DOI":"10.3390\/ijms21197113","volume":"21","author":"G Kouroupi","year":"2020","unstructured":"Kouroupi G, Antoniou N, Prodromidou K, Taoufik E, Matsas R (2020) Patient-derived induced pluripotent stem cell-based models in Parkinson\u2019s disease for drug identification. Int J Mol Sci 21(19):7113. https:\/\/doi.org\/10.3390\/ijms21197113","journal-title":"Int J Mol Sci"},{"key":"1907_CR31","volume-title":"Mass Spectrometry Analysis Reveals Sequence and Higher-Order Structure Information for Proteins and Protein Complexes","author":"C Lantz","year":"2022","unstructured":"Lantz C (2022) Mass Spectrometry Analysis Reveals Sequence and Higher-Order Structure Information for Proteins and Protein Complexes. University of California, Los Angeles"},{"issue":"7","key":"1907_CR32","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.3390\/ijms25073929","volume":"25","author":"P Lenzi","year":"2024","unstructured":"Lenzi P, Lazzeri G, Ferrucci M, Scotto M, Frati A, Puglisi-Allegra S, Busceti CL, Fornai F (2024) Is there a place for Lewy bodies before and beyond alpha-synuclein accumulation? Provocative issues in need of solid explanations. Int J Mol Sci 25(7):3929. https:\/\/doi.org\/10.3390\/ijms25073929","journal-title":"Int J Mol Sci"},{"issue":"4","key":"1907_CR74","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.3233\/jad-160033","volume":"52","author":"X Li","year":"2016","unstructured":"Li X, Song Y, Sanders CR, Buxbaum JN (2016) Transthyretin suppresses amyloid-\u03b2 secretion by interfering with processing of the amyloid-\u03b2 protein precursor. J Alzheimer\u2019s Disease 52(4):1263\u20131275. https:\/\/doi.org\/10.3233\/jad-160033","journal-title":"J Alzheimer\u2019s Disease"},{"issue":"2","key":"1907_CR70","doi-asserted-by":"publisher","first-page":"262","DOI":"10.17305\/bb.2025.12931","volume":"26","author":"S Liu","year":"2025","unstructured":"Liu S, Liang Q (2025) Sepsis toxicity network reconstruction\u2014Dynamic signaling and multi-organ injury: A review. Biomolecules Biomed 26(2):262. https:\/\/doi.org\/10.17305\/bb.2025.12931","journal-title":"Biomolecules Biomed"},{"issue":"20","key":"1907_CR35","doi-asserted-by":"publisher","first-page":"21431","DOI":"10.1074\/jbc.M402212200","volume":"279","author":"MA Liz","year":"2004","unstructured":"Liz MA, Faro CJ, Saraiva MJ, Sousa MM (2004) Transthyretin, a new cryptic protease. J Biol Chem 279(20):21431\u201321438. https:\/\/doi.org\/10.1074\/jbc.M402212200","journal-title":"J Biol Chem"},{"issue":"2","key":"1907_CR34","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s40120-020-00217-0","volume":"9","author":"MA Liz","year":"2020","unstructured":"Liz MA, Coelho T, Bellotti V, Fernandez-Arias MI, Mallaina P, Obici L (2020) A narrative review of the role of transthyretin in health and disease. Neurol therapy 9(2):395\u2013402. https:\/\/doi.org\/10.1007\/s40120-020-00217-0","journal-title":"Neurol therapy"},{"issue":"2","key":"1907_CR36","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s12017-017-8454-x","volume":"19","author":"FM Lopes","year":"2017","unstructured":"Lopes FM, Bristot IJ, Da Motta LL, Parsons RB, Klamt F (2017) Mimicking Parkinson\u2019s disease in a dish: merits and pitfalls of the most commonly used dopaminergic in vitro models. Neuromol Med 19(2):241\u2013255. https:\/\/doi.org\/10.1007\/s12017-017-8454-x","journal-title":"Neuromol Med"},{"issue":"1","key":"1907_CR68","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1038\/s41467-018-04422-2","volume":"9","author":"MH Ludtmann","year":"2018","unstructured":"Ludtmann MH, Angelova PR, Horrocks MH, Choi ML, Rodrigues M, Baev AY, Berezhnov AV, Yao Z, Little D, Banushi B, Al-Menhali AS (2018) \u03b1-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson\u2019s disease. Nat Commun 9(1):2293. https:\/\/doi.org\/10.1038\/s41467-018-04422-2","journal-title":"Nat Commun"},{"key":"1907_CR37","doi-asserted-by":"publisher","first-page":"1498756","DOI":"10.3389\/fnagi.2024.1498756","volume":"16","author":"Y Luo","year":"2025","unstructured":"Luo Y, Qiao L, Li M, Wen X, Zhang W, Li X (2025) Global, regional, national epidemiology and trends of Parkinson\u2019s disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. Front Aging Neurosci 16:1498756. https:\/\/doi.org\/10.3389\/fnagi.2024.1498756","journal-title":"Front Aging Neurosci"},{"issue":"33","key":"1907_CR38","doi-asserted-by":"publisher","first-page":"E7710","DOI":"10.1073\/pnas.1801117115","volume":"115","author":"K Madhivanan","year":"2018","unstructured":"Madhivanan K, Greiner ER, Alves-Ferreira M, Soriano-Castell D, Rouzbeh N, Aguirre CA, Paulsson JF, Chapman J, Jiang X, Ooi FK, Lemos C (2018) Cellular clearance of circulating transthyretin decreases cell-nonautonomous proteotoxicity in Caenorhabditis elegans. Proceedings of the National Academy of Sciences 115(33):E7710-9. https:\/\/doi.org\/10.1073\/pnas.1801117115","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"10","key":"1907_CR39","doi-asserted-by":"publisher","first-page":"e48042","DOI":"10.1371\/journal.pone.0048042","volume":"7","author":"W Maetzler","year":"2012","unstructured":"Maetzler W, Tian Y, Baur SM, Gauger T, Odoj B, Schmid B, Schulte C, Deuschle C, Heck S, Apel A, Melms A (2012) Serum and cerebrospinal fluid levels of transthyretin in Lewy body disorders with and without dementia. PLoS ONE 7(10):e48042. https:\/\/doi.org\/10.1371\/journal.pone.0048042","journal-title":"PLoS ONE"},{"key":"1907_CR12","doi-asserted-by":"crossref","unstructured":"Magalh\u00e3es J, Eira J Liz MA (2021) The role of transthyretin in cell biology: impact on human pathophysiology. Cell Mol Life Sci 78(17-18):6105\u20136117","DOI":"10.1007\/s00018-021-03899-3"},{"issue":"11","key":"1907_CR40","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1056\/nejmoa1805689","volume":"379","author":"MS Maurer","year":"2018","unstructured":"Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM (2018) Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 379(11):1007\u20131016. https:\/\/doi.org\/10.1056\/nejmoa1805689","journal-title":"N Engl J Med"},{"key":"1907_CR41","doi-asserted-by":"publisher","first-page":"852003","DOI":"10.3389\/fneur.2022.852003","volume":"13","author":"S Menon","year":"2022","unstructured":"Menon S, Armstrong S, Hamzeh A, Visanji NP, Sardi SP, Tandon A (2022) Alpha-synuclein targeting therapeutics for Parkinson\u2019s disease and related synucleinopathies. Front Neurol 13:852003. https:\/\/doi.org\/10.3389\/fneur.2022.852003","journal-title":"Front Neurol"},{"issue":"2","key":"1907_CR43","doi-asserted-by":"publisher","first-page":"986","DOI":"10.3390\/ijms25020986","volume":"25","author":"K Nordengen","year":"2024","unstructured":"Nordengen K, Morland C (2024) From synaptic physiology to synaptic pathology: the enigma of \u03b1-synuclein. Int J Mol Sci 25(2):986. https:\/\/doi.org\/10.3390\/ijms25020986","journal-title":"Int J Mol Sci"},{"issue":"7","key":"1907_CR44","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1002\/humu.21277","volume":"31","author":"K Nuytemans","year":"2010","unstructured":"Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C (2010) Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat 31(7):763\u2013780. https:\/\/doi.org\/10.1002\/humu.21277","journal-title":"Hum Mutat"},{"key":"1907_CR77","doi-asserted-by":"crossref","unstructured":"Peng C, Gathagan RJ, Lee VMY (2018) Distinct \u03b1-Synuclein strains and implications for heterogeneity among \u03b1-Synucleinopathies. Neurobiol Dis 109:209\u2013218","DOI":"10.1016\/j.nbd.2017.07.018"},{"key":"1907_CR45","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/978-3-7091-0932-8_24","volume":"27","author":"B Picconi","year":"2012","unstructured":"Picconi B, Piccoli G, Calabresi P (2012) Synaptic dysfunction in Parkinson\u2019s disease. Synaptic Plasticity: Dynamics Dev Disease 27:553\u2013572. https:\/\/doi.org\/10.1007\/978-3-7091-0932-8_24","journal-title":"Synaptic Plasticity: Dynamics Dev Disease"},{"key":"1907_CR47","doi-asserted-by":"publisher","unstructured":"Rao R (2008) Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Frontiers in bioscience: a journal and virtual library 13:7210. https:\/\/doi.org\/10.2741\/3223","DOI":"10.2741\/3223"},{"key":"1907_CR48","doi-asserted-by":"publisher","unstructured":"Robertson KV, Rodriguez AS, Cartailler JP, Shrestha S, Schroeder KR, Valenti AM, Harrison FE, Hasty AH (2024) Knockdown of microglial iron import gene, DMT1, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP\/PS1 model of Alzheimer\u2019s disease. Res Square 27:rs\u20133. https:\/\/doi.org\/10.1186\/s12974-024-03238-w","DOI":"10.1186\/s12974-024-03238-w"},{"issue":"10","key":"1907_CR75","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1161\/circulationaha.111.078915","volume":"126","author":"FL Ruberg","year":"2012","unstructured":"Ruberg FL, Berk JL (2012) Transthyretin (TTR) cardiac amyloidosis. Circulation 126(10):1286\u20131300. https:\/\/doi.org\/10.1161\/circulationaha.111.078915","journal-title":"Circulation"},{"key":"1907_CR50","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1101\/2023.08.10.552896","volume":"11","author":"Z S\u00e1rk\u00e1ny","year":"2023","unstructured":"S\u00e1rk\u00e1ny Z, Gi\u00e3o T, Liz MA, Planas A, Macedo-Ribeiro S, Cardoso I, Arsequell G, Martins PM (2023) Transthyretin has conformation-selective proteolytic activity against \u03b1-synuclein. bioRxiv 11:2023\u20132008. https:\/\/doi.org\/10.1101\/2023.08.10.552896","journal-title":"bioRxiv"},{"issue":"8","key":"1907_CR49","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.3390\/biomedicines10081906","volume":"10","author":"C Sanguinetti","year":"2022","unstructured":"Sanguinetti C, Minniti M, Susini V, Caponi L, Panichella G, Castiglione V, Aimo A, Emdin M, Vergaro G, Franzini M (2022) The journey of human transthyretin: synthesis, structure stability, and catabolism. Biomedicines 10(8):1906. https:\/\/doi.org\/10.3390\/biomedicines10081906","journal-title":"Biomedicines"},{"issue":"3","key":"1907_CR51","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1111\/j.1468-1331.2009.02841.x","volume":"17","author":"K Schultz","year":"2010","unstructured":"Schultz K, Nilsson K, Nielsen JE, Lindquist SG, Hjermind LE, Andersen BB, Wallin A, Nilsson C, Peters\u00e9n \u00c5 (2010) Transthyretin as a potential CSF biomarker for Alzheimer\u2019s disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors. Eur J Neurol 17(3):456\u2013460. https:\/\/doi.org\/10.1111\/j.1468-1331.2009.02841.x","journal-title":"Eur J Neurol"},{"key":"1907_CR20","doi-asserted-by":"crossref","unstructured":"Sekijima Y (2015) Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry 86(9):1036\u20131043","DOI":"10.1136\/jnnp-2014-308724"},{"key":"1907_CR30","doi-asserted-by":"crossref","unstructured":"Sharma M, Khan S, Rahman S, Singh LR (2019) The extracellular protein, transthyretin is an oxidative stress biomarker. Front Physiol 10:5","DOI":"10.3389\/fphys.2019.00005"},{"issue":"1","key":"1907_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11033-025-10485-4","volume":"52","author":"S Shaw","year":"2025","unstructured":"Shaw S, Porel P, Aran KR (2025) Transthyretin as a therapeutic target: the future of disease-modifying therapies for Alzheimer\u2019s disease. Mol Biol Rep 52(1):1\u20136. https:\/\/doi.org\/10.1007\/s11033-025-10485-4","journal-title":"Mol Biol Rep"},{"issue":"8","key":"1907_CR53","doi-asserted-by":"publisher","first-page":"743","DOI":"10.3390\/antiox9080743","volume":"9","author":"DS Simpson","year":"2020","unstructured":"Simpson DS, Oliver PL (2020) ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants 9(8):743. https:\/\/doi.org\/10.3390\/antiox9080743","journal-title":"Antioxidants"},{"issue":"1","key":"1907_CR54","doi-asserted-by":"publisher","first-page":"4356386","DOI":"10.1155\/2020\/4356386","volume":"2020","author":"K Song","year":"2020","unstructured":"Song K, Li Y, Zhang H, An N, Wei Y, Wang L, Tian C, Yuan M, Sun Y, Xing Y, Gao Y (2020) Oxidative stress-mediated blood\u2010brain barrier (BBB) disruption in neurological diseases. Oxidative Med Cell Longev 2020(1):4356386. https:\/\/doi.org\/10.1155\/2020\/4356386","journal-title":"Oxidative Med Cell Longev"},{"key":"1907_CR55","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.70188","author":"F Stocchi","year":"2025","unstructured":"Stocchi F, Kulisevsky J, Jost WH (2025) A real-world study on unstable Parkinson\u2019s disease: levodopa dosage management and the role of nonmotor symptoms. Mov Disord Clin Pract. https:\/\/doi.org\/10.1002\/mdc3.70188","journal-title":"Mov Disord Clin Pract"},{"issue":"3","key":"1907_CR56","doi-asserted-by":"publisher","first-page":"249","DOI":"10.2174\/0118715249287167240222081517","volume":"24","author":"I Subhan","year":"2024","unstructured":"Subhan I, Siddique YH, Resveratrol (2024) Protective agent against Alzheimer\u2019s disease. Central Nervous System Agents in Medicinal ChemistryChemistry-Central Nervous System Agents). 24(3):249\u2013263. https:\/\/doi.org\/10.2174\/0118715249287167240222081517","journal-title":"Central Nervous System Agents in Medicinal ChemistryChemistry-Central Nervous System Agents)"},{"issue":"2","key":"1907_CR57","doi-asserted-by":"publisher","first-page":"202400249","DOI":"10.1002\/cptc.202400249in","volume":"9","author":"M Sundnes","year":"2025","unstructured":"Sundnes M, Swaminathan P, Lindgren M, Mohite G, Hellstrand E, Nystr\u00f6m S, Hammarstr\u00f6m P (2025) The fluorescent amyloid ligand X34 binding to transthyretin (TTR) tetramer and fibrils: FRET and binding constants of a sequential two-step process. ChemPhotoChem 9(2):202400249. https:\/\/doi.org\/10.1002\/cptc.202400249in","journal-title":"ChemPhotoChem"},{"key":"1907_CR58","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017","author":"MD Sweeney","year":"2018","unstructured":"Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2018) Blood\u2013brain barrier: from physiology to disease and back. Physiol Rev. https:\/\/doi.org\/10.1152\/physrev.00050.2017","journal-title":"Physiol Rev"},{"issue":"6","key":"1907_CR71","doi-asserted-by":"publisher","first-page":"761","DOI":"10.3727\/096368914X680073","volume":"23","author":"YD Teng","year":"2014","unstructured":"Teng YD (2014) For neural therapy and repair. Cell Transpl 23(6):761\u2013790. https:\/\/doi.org\/10.3727\/096368914X680073","journal-title":"Cell Transpl"},{"key":"1907_CR59","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fnmol.2018.00049","volume":"11","author":"J Tol\u00f6","year":"2018","unstructured":"Tol\u00f6 J, Taschenberger G, Leite K, Stahlberg MA, Spehlbrink G, Kues J, Munari F, Capaldi S, Becker S, Zweckstetter M, Dean C (2018) Pathophysiological consequences of neuronal \u03b1-Synucleinoverexpression: impacts on ion homeostasis, stress signaling, mitochondrial integrity, and electrical activity. Front Mol Neurosci 11:49. https:\/\/doi.org\/10.3389\/fnmol.2018.00049","journal-title":"Front Mol Neurosci"},{"key":"1907_CR42","doi-asserted-by":"crossref","unstructured":"Trist BG, Hare DJ, Double KL (2019) Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease. Aging Cell 18(6):e13031","DOI":"10.1111\/acel.13031"},{"issue":"11","key":"1907_CR60","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.3390\/cells11111732","volume":"11","author":"M Vidovi\u0107","year":"2022","unstructured":"Vidovi\u0107 M, Rikalovic MG (2022) Alpha-synuclein aggregation pathway in Parkinson\u2019s disease: current status and novel therapeutic approaches. Cells 11(11):1732. https:\/\/doi.org\/10.3390\/cells11111732","journal-title":"Cells"},{"issue":"1","key":"1907_CR61","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1515\/bmc-2013-0038","volume":"5","author":"M Vieira","year":"2014","unstructured":"Vieira M, Saraiva MJ (2014) Transthyretin: a multifaceted protein. Biomol Concepts 5(1):45\u201354. https:\/\/doi.org\/10.1515\/bmc-2013-0038","journal-title":"Biomol Concepts"},{"key":"1907_CR62","doi-asserted-by":"publisher","first-page":"10","DOI":"10.4103\/nrr.nrr-d-25-00107","volume":"3","author":"J Wang","year":"2025","unstructured":"Wang J, Du W, Chen X, Wu H, Liu G (2025) Hypoxia and TTR dysregulation in astrocytes from Parkinson\u2019s disease with a specific mitochondrial haplogroup: A single-cell analysis. Neural Regeneration Res 3:10\u20134103. https:\/\/doi.org\/10.4103\/nrr.nrr-d-25-00107","journal-title":"Neural Regeneration Res"},{"key":"1907_CR63","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3389\/fnmol.2018.00236","volume":"11","author":"Z Wei","year":"2018","unstructured":"Wei Z, Li X, Li X, Liu Q, Cheng Y (2018) Oxidative stress in Parkinson\u2019s disease: a systematic review and meta-analysis. Front Mol Neurosci 11:236. https:\/\/doi.org\/10.3389\/fnmol.2018.00236","journal-title":"Front Mol Neurosci"},{"key":"1907_CR64","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3389\/fnmol.2019.00271","volume":"12","author":"C Wells","year":"2019","unstructured":"Wells C, Brennan SE, Keon M, Saksena NK (2019) Prionoid proteins in the pathogenesis of neurodegenerative diseases. Front Mol Neurosci 12:271. https:\/\/doi.org\/10.3389\/fnmol.2019.00271","journal-title":"Front Mol Neurosci"},{"key":"1907_CR26","doi-asserted-by":"crossref","unstructured":"Wennstr\u00f6m M, Surova Y, Hall S, Nilsson C, Minthon L, Bostr\u00f6m F, Hansson O, Nielsen HM (2013) Low CSF levels of both \u03b1-synuclein and the \u03b1-synuclein cleaving enzyme neurosin in patients with synucleinopathy. PloS one 8(1):e53250","DOI":"10.1371\/journal.pone.0053250"},{"issue":"7","key":"1907_CR65","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.3390\/cells10071768","volume":"10","author":"E Wieczorek","year":"2021","unstructured":"Wieczorek E, O\u017cyhar A (2021) Transthyretin: from structural stability to osteoarticular and cardiovascular diseases. Cells 10(7):1768. https:\/\/doi.org\/10.3390\/cells10071768","journal-title":"Cells"},{"issue":"6","key":"1907_CR66","doi-asserted-by":"publisher","first-page":"790","DOI":"10.3390\/ph18060790","volume":"18","author":"G Xie","year":"2025","unstructured":"Xie G, Jiang G, Huang L, Sun S, Wan Y, Li F, Wu B, Zhang Y, Li X, Xiong B, Xiong J (2025) The Role of APOA-I in Alzheimer\u2019s Disease: Bridging Peripheral Tissues and the Central Nervous System. Pharmaceuticals 18(6):790. https:\/\/doi.org\/10.3390\/ph18060790","journal-title":"Pharmaceuticals"},{"issue":"21","key":"1907_CR67","doi-asserted-by":"publisher","first-page":"11409","DOI":"10.3390\/ijms252111409","volume":"25","author":"K Zgutka","year":"2024","unstructured":"Zgutka K, Tkacz M, Tomasiak P, Piotrowska K, Ustianowski P, Pawlik A, Tarnowski M (2024) Gestational diabetes mellitus-induced inflammation in the placenta via IL-1\u03b2 and toll-like receptor pathways. Int J Mol Sci 25(21):11409. https:\/\/doi.org\/10.3390\/ijms252111409","journal-title":"Int J Mol Sci"}],"container-title":["Metabolic Brain Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-026-01907-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11011-026-01907-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-026-01907-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:59:08Z","timestamp":1783407548000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11011-026-01907-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1907"],"URL":"https:\/\/doi.org\/10.1007\/s11011-026-01907-8","relation":{},"ISSN":["1573-7365"],"issn-type":[{"value":"1573-7365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"10 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 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":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"157"}}