{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T11:14:12Z","timestamp":1794222852798,"version":"4.8.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-162364"],"award-info":[{"award-number":["PJT-162364"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Sciences and Engineering Research","award":["RGPIN\/04998-2017"],"award-info":[{"award-number":["RGPIN\/04998-2017"]}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["CRC-2021-00117"],"award-info":[{"award-number":["CRC-2021-00117"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins\/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer\u2019s disease, diabetes, AL\/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the \u03b2-amyloid (1\u201342) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.<\/jats:p>","DOI":"10.1038\/s41598-023-41712-2","type":"journal-article","created":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T14:01:35Z","timestamp":1693663295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Stress-mediated aggregation of disease-associated proteins in amyloid bodies"],"prefix":"10.1038","volume":"13","author":[{"given":"Sahil","family":"Chandhok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia A.","family":"Momchilova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Marijan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Zapf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Lacroix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avneet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayan","family":"Keymanesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Krieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E.","family":"Audas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,2]]},"reference":[{"key":"41712_CR1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","volume":"75","author":"F Chiti","year":"2006","unstructured":"Chiti, F. & Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333\u2013366 (2006).","journal-title":"Annu. Rev. Biochem."},{"key":"41712_CR2","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4161\/pri.2.3.7488","volume":"2","author":"RN Rambaran","year":"2008","unstructured":"Rambaran, R. N. & Serpell, L. C. Amyloid fibrils: Abnormal protein assembly. Prion 2, 112\u2013117 (2008).","journal-title":"Prion"},{"key":"41712_CR3","doi-asserted-by":"crossref","first-page":"15806","DOI":"10.1073\/pnas.0604035103","volume":"103","author":"JF Smith","year":"2006","unstructured":"Smith, J. F., Knowles, T. P. J., Dobson, C. M., Macphee, C. E. & Welland, M. E. Characterization of the nanoscale properties of individual amyloid fibrils. PNAS 103, 15806\u201315811 (2006).","journal-title":"PNAS"},{"key":"41712_CR4","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/s41580-018-0060-8","volume":"19","author":"MG Iadanza","year":"2018","unstructured":"Iadanza, M. G., Jackson, M. P., Hewitt, E. W., Ranson, N. A. & Radford, S. E. A new era for understanding amyloid structures and disease. Nat. Rev. Mol. Cell Biol. 19, 755\u2013773 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"41712_CR5","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s12551-017-0353-8","volume":"10","author":"E Chatani","year":"2018","unstructured":"Chatani, E. & Yamamoto, N. Recent progress on understanding the mechanisms of amyloid nucleation. Biophys. Rev. 10, 527\u2013534 (2018).","journal-title":"Biophys. Rev."},{"key":"41712_CR6","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1016\/j.bpj.2010.10.039","volume":"99","author":"B Morel","year":"2010","unstructured":"Morel, B., Varela, L., Azuaga, A. I. & Conejero-lara, F. Environmental conditions affect the kinetics of nucleation of amyloid fibrils and determine their morphology. Biophys. J. 99, 3801\u20133810 (2010).","journal-title":"Biophys. J."},{"key":"41712_CR7","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jmb.2004.06.020","volume":"341","author":"JS Pedersen","year":"2004","unstructured":"Pedersen, J. S., Christensen, G. & Otzen, D. E. Modulation of S6 fibrillation by unfolding rates and gatekeeper residues. J. Mol. Biol. 341, 575\u2013588 (2004).","journal-title":"J. Mol. Biol."},{"key":"41712_CR8","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.cell.2012.02.022","volume":"148","author":"D Eisenberg","year":"2012","unstructured":"Eisenberg, D. & Jucker, M. The amyloid state of proteins in human diseases. Cell 148, 1188\u20131203 (2012).","journal-title":"Cell"},{"key":"41712_CR9","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.bbamem.2018.02.022","volume":"1860","author":"MFM Sciacca","year":"2018","unstructured":"Sciacca, M. F. M., Tempra, C., Scollo, F., Milardi, D. & La, C. Amyloid growth and membrane damage: Current themes and emerging perspectives from theory and experiments on A\u03b2 and hIAPP. BBA Biomembr. 1860, 1625\u20131638 (2018).","journal-title":"BBA Biomembr."},{"key":"41712_CR10","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.neurobiolaging.2007.04.014","volume":"29","author":"BP Tseng","year":"2008","unstructured":"Tseng, B. P., Green, K. N., Chan, J. L., Blurton-jones, M. & Frank, M. A\u03b2 inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol. Aging 29, 1607\u20131618 (2008).","journal-title":"Neurobiol. Aging"},{"key":"41712_CR11","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.2174\/1568026611212220007","volume":"12","author":"M Ramirez-Alvarado","year":"2012","unstructured":"Ramirez-Alvarado, M. Amyloid formation in light chain amyloidosis. Curr. Top. Med. Chem. 12, 2523\u20132533 (2012).","journal-title":"Curr. Top. Med. Chem."},{"key":"41712_CR12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/bs.ircmb.2017.07.002","volume":"336","author":"C Ntsapi","year":"2018","unstructured":"Ntsapi, C., Lumkwana, D., Swart, C., du Toit, A. & Loos, B. New insights into autophagy dysfunction related to amyloid beta toxicity and neuropathology in Alzheimer\u2019s disease. Int. Rev. Cell Mol. Biol. 336, 321\u201361 (2018).","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"41712_CR13","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1093\/hmg\/3.6.981","volume":"3","author":"DR Rosen","year":"1994","unstructured":"Rosen, D. R. et al. A frequent ala 4 to val superoxide dismutase-1 mutation is associated with a rapidly progressive familial amyotrophic lateral sclerosis. Hum. Mol. Genet. 3, 981\u2013987 (1994).","journal-title":"Hum. Mol. Genet."},{"key":"41712_CR14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-neuro-061010-113613","volume":"34","author":"RJ O\u2019Brien","year":"2011","unstructured":"O\u2019Brien, R. J. & Wong, P. C. Amyloid precursor protein processing and Alzheimer\u2019s disease. Annu Rev Neurosci 34, 185\u2013204 (2011).","journal-title":"Annu Rev Neurosci"},{"key":"41712_CR15","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1046\/j.1471-4159.1998.71052041.x","volume":"71","author":"PK Andrus","year":"1998","unstructured":"Andrus, P. K., Fleck, T. J., Gurney, M. E. & Hall, E. D. Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 71, 2041\u20132048 (1998).","journal-title":"J. Neurochem."},{"key":"41712_CR16","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.febslet.2013.01.017","volume":"587","author":"A Abedini","year":"2015","unstructured":"Abedini, A. & Schmidt, A. M. Mechanisms of islet amyloidosis toxicity in type 2 diabetes. FEBS Lett. 587, 1119\u20131127 (2015).","journal-title":"FEBS Lett."},{"key":"41712_CR17","doi-asserted-by":"crossref","first-page":"3694","DOI":"10.1093\/brain\/awr300","volume":"134","author":"M Garcia-Alloza","year":"2011","unstructured":"Garcia-Alloza, M. et al. Cerebrovascular lesions induce transient beta-amyloid deposition. Brain 134, 3694\u20133704 (2011).","journal-title":"Brain"},{"key":"41712_CR18","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s00401-001-0487-3","volume":"103","author":"R Sinigaglia-Coimbra","year":"2002","unstructured":"Sinigaglia-Coimbra, R., Cavalheiro, E. A. & Coimbra, C. G. Postischemic hyperthermia induces Alzheimer-like pathology in the rat brain. Acta Neuropathol. 103, 444\u2013452 (2002).","journal-title":"Acta Neuropathol."},{"key":"41712_CR19","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","volume":"4","author":"JW Kinney","year":"2018","unstructured":"Kinney, J. W. et al. Inflammation as a central mechanism in Alzheimer\u2019s disease. Alzheimer\u2019s Dement. Transl. Res. Clin. Interv. 4, 575\u2013590 (2018).","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"41712_CR20","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.tcb.2017.03.001","volume":"27","author":"M Wang","year":"2017","unstructured":"Wang, M., Audas, T. E. & Lee, S. Disentangling a bad reputation: Changing perceptions of amyloids. Trends Cell Biol. 27, 465\u2013467 (2017).","journal-title":"Trends Cell Biol."},{"key":"41712_CR21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01148.x","author":"EA Epstein","year":"2008","unstructured":"Epstein, E. A. & Chapman, M. R. Polymerizing the fibre between bacteria and host cells: the biogenesis of functional amyloid fibres Amyloid: A convergence of diverse proteins along a common folding pathway. Cell Microbiol. https:\/\/doi.org\/10.1111\/j.1462-5822.2008.01148.x (2008).","journal-title":"Cell Microbiol."},{"issue":"5","key":"41712_CR22","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.tibs.2007.03.003","volume":"32","author":"DM Fowler","year":"2007","unstructured":"Fowler, D. M., Koulov, A. V., Balch, W. E. & Kelly, J. W. Functional amyloid\u2014from bacteria to humans. Trends Biochem. Sci. 32(5), 217\u2013224 (2007).","journal-title":"Trends Biochem. Sci."},{"key":"41712_CR23","doi-asserted-by":"publisher","DOI":"10.1242\/bio.017384","author":"MH Hayes","year":"2016","unstructured":"Hayes, M. H. & Weeks, D. L. Amyloids assemble as part of recognizable structures during oogenesis in Xenopus. Biol. Open https:\/\/doi.org\/10.1242\/bio.017384 (2016).","journal-title":"Biol. Open"},{"key":"41712_CR24","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cell.2012.06.019","volume":"150","author":"J Li","year":"2012","unstructured":"Li, J. et al. The RIP1\/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150, 339\u2013350 (2012).","journal-title":"Cell"},{"key":"41712_CR25","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1126\/science.1173155","volume":"325","author":"SK Maji","year":"2010","unstructured":"Maji, S. K. et al. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325, 328\u2013332 (2010).","journal-title":"Science"},{"key":"41712_CR26","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3390\/ijms17091438","volume":"17","author":"C Bissig","year":"2016","unstructured":"Bissig, C., Rochin, L. & Niel, G. V. PMEL amyloid fibril formation: The bright steps of pigmentation. Int. J. Mol. Sci. 17, 1438 (2016).","journal-title":"Int. J. Mol. Sci."},{"key":"41712_CR27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.devcel.2016.09.002","volume":"39","author":"TE Audas","year":"2016","unstructured":"Audas, T. E. et al. Adaptation to stressors by systemic protein amyloidogenesis. Dev. Cell 39, 155\u2013168 (2016).","journal-title":"Dev. Cell"},{"key":"41712_CR28","doi-asserted-by":"crossref","first-page":"jcs258907","DOI":"10.1242\/jcs.258907","volume":"134","author":"E Lacroix","year":"2021","unstructured":"Lacroix, E. et al. Evolutionary conservation of systemic and reversible amyloid aggregation. J. Cell Sci. 134, jcs258907 (2021).","journal-title":"J. Cell Sci."},{"key":"41712_CR29","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13597","author":"D Marijan","year":"2019","unstructured":"Marijan, D. et al. Stress-specific aggregation of proteins in the amyloid bodies. FEBS Lett. https:\/\/doi.org\/10.1002\/1873-3468.13597 (2019).","journal-title":"FEBS Lett."},{"key":"41712_CR30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmolb.2022.998363","volume":"9","author":"E Lacroix","year":"2022","unstructured":"Lacroix, E. & Audas, T. E. Keeping up with the condensates: The retention, gain, and loss of nuclear membrane-less organelles. Front. Mol. Biosci. 9, 1\u201317 (2022).","journal-title":"Front. Mol. Biosci."},{"key":"41712_CR31","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1091\/mbc.e13-04-0223","volume":"24","author":"MD Jacob","year":"2013","unstructured":"Jacob, M. D., Audas, T. E., Uniacke, J., Trinkle-Mulcahy, L. & Lee, S. Environmental cues induce a long noncoding RNA-dependent remodeling of the nucleolus. Mol. Biol. Cell 24, 2943\u20132953 (2013).","journal-title":"Mol. Biol. Cell"},{"key":"41712_CR32","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1093\/hmg\/ddt117","volume":"22","author":"C Vance","year":"2013","unstructured":"Vance, C. et al. ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules. Hum. Mol. Genet. 22, 2676\u20132688 (2013).","journal-title":"Hum. Mol. Genet."},{"key":"41712_CR33","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.020099","author":"J Lenzi","year":"2015","unstructured":"Lenzi, J. et al. ALS mutant FUS proteins are recruited into stress granules in induced Pluripotent Stem Cells (iPSCs) derived motoneurons. Dis. Model. Mech. https:\/\/doi.org\/10.1242\/dmm.020099 (2015).","journal-title":"Dis. Model. Mech."},{"key":"41712_CR34","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.neuron.2017.07.025","volume":"95","author":"IR Mackenzie","year":"2017","unstructured":"Mackenzie, I. R. et al. TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics. Neuron 95, 808-816.e9 (2017).","journal-title":"Neuron"},{"key":"41712_CR35","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1093\/hmg\/ddt622","volume":"23","author":"TA Shelkovnikova","year":"2014","unstructured":"Shelkovnikova, T. A., Robinson, H. K., Troakes, C., Ninkina, N. & Buchman, V. L. Compromised paraspeckle formation as a pathogenic factor in FUSopathies. Hum. Mol. Genet. 23, 2298\u20132312 (2014).","journal-title":"Hum. Mol. Genet."},{"key":"41712_CR36","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1747-4949.2011.00666.x","volume":"6","author":"TB Cumming","year":"2011","unstructured":"Cumming, T. B. & Brodtmann, A. Can stroke cause neurodegenerative dementia?. Int. J. Stroke 6, 416\u2013424 (2011).","journal-title":"Int. J. Stroke"},{"key":"41712_CR37","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3233\/JAD-160527","volume":"54","author":"M Vijayan","year":"2016","unstructured":"Vijayan, M. & Reddy, P. H. Stroke, vascular dementia, and Alzheimer\u2019s disease: Molecular links. J. Alzheimer\u2019s Dis. 54, 427\u2013443 (2016).","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"41712_CR38","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1001\/archneur.60.12.1707","volume":"60","author":"LS Honig","year":"2003","unstructured":"Honig, L. S. et al. Stroke and the risk of Alzheimer disease. Arch. Neurol. 60, 1707 (2003).","journal-title":"Arch. Neurol."},{"key":"41712_CR39","first-page":"1","volume":"202200216","author":"B Xu","year":"2022","unstructured":"Xu, B., Mo, X., Chen, J., Yu, H. & Liu, Y. Myricetin inhibits \u03b1-synuclein amyloid aggregation by delaying the liquid-to-solid phase transition. ChemBioChem 202200216, 1\u20138 (2022).","journal-title":"ChemBioChem"},{"key":"41712_CR40","doi-asserted-by":"crossref","first-page":"21497","DOI":"10.1021\/acsomega.0c02063","volume":"5","author":"G Park","year":"2020","unstructured":"Park, G., Xue, C., Wang, H. & Guo, Z. Distinguishing the effect on the rate and yield of A\u03b242 aggregation by green tea polyphenol EGCG. ACS Omega 5, 21497\u201321505 (2020).","journal-title":"ACS Omega"},{"key":"41712_CR41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-3-319-18365-7_7","volume":"863","author":"K Andrich","year":"2015","unstructured":"Andrich, K. & Bieschke, J. The effect of (-)-epigallo-catechin-(3)-gallate on amyloidogenic proteins suggests a common mechanism. Adv. Exp. Med. Biol. 863, 139\u201361 (2015).","journal-title":"Adv. Exp. Med. Biol."},{"key":"41712_CR42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/nu12113480","volume":"12","author":"K Ogawa","year":"2020","unstructured":"Ogawa, K. et al. Spearmint extract containing rosmarinic acid suppresses amyloid fibril formation of proteins associated with dementia. Nutrients 12, 1\u201314 (2020).","journal-title":"Nutrients"},{"key":"41712_CR43","first-page":"1","volume":"14","author":"J Sun","year":"2019","unstructured":"Sun, J., Jiang, G. & Shigemori, H. Inhibitory activity on amyloid aggregation of rosmarinic acid and its substructures from Isodon Japonicus. Nat. Prod. Commun. 14, 1\u20135 (2019).","journal-title":"Nat. Prod. Commun."},{"key":"41712_CR44","doi-asserted-by":"crossref","first-page":"175628642093567","DOI":"10.1177\/1756286420935676","volume":"13","author":"O Stuve","year":"2020","unstructured":"Stuve, O., Weideman, R. A., McMahan, D. M., Jacob, D. A. & Little, B. B. Diclofenac reduces the risk of Alzheimer\u2019s disease: A pilot analysis of NSAIDs in two US veteran populations. Ther. Adv. Neurol. Disord. 13, 175628642093567 (2020).","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"41712_CR45","first-page":"1","volume":"8","author":"J Chu","year":"2013","unstructured":"Chu, J., Li, J. G. & Pratic\u00f2, D. Zileuton improves memory deficits, amyloid and tau pathology in a mouse model of Alzheimer\u2019s disease with plaques and tangles. PLoS ONE 8, 1\u20138 (2013).","journal-title":"PLoS ONE"},{"key":"41712_CR46","first-page":"1","volume":"8","author":"SL Booth","year":"2022","unstructured":"Booth, S. L. et al. Association of vitamin K with cognitive decline and neuropathology in community-dwelling older persons. Alzheimer\u2019s Dement. Transl. Res. Clin. Interv. 8, 1\u20139 (2022).","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"41712_CR47","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1471-4159.2008.05412.x","volume":"106","author":"NA Dorofeeva","year":"2008","unstructured":"Dorofeeva, N. A., Barygin, O. I., Staruschenko, A., Bolshakov, K. V. & Magazanik, L. G. Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneurons. J. Neurochem. 106, 429\u2013441 (2008).","journal-title":"J. Neurochem."},{"key":"41712_CR48","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1021\/jm0613166","volume":"50","author":"AL Blobaum","year":"2007","unstructured":"Blobaum, A. L. & Marnett, L. J. Structural and functional basis of cyclooxygenase inhibition. J. Med. Chem. 50, 1425\u20131441 (2007).","journal-title":"J. Med. Chem."},{"key":"41712_CR49","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4062\/biomolther.2020.090","volume":"28","author":"F Jin","year":"2020","unstructured":"Jin, F., Li, X., Lee, H. J. & Lee, C. J. Diclofenac inhibits phorbol ester-induced gene expression and production of muc5ac mucin via affecting degradation of ikb\u03b1 and translocation of nf-kb p65 in nci-h292 cells. Biomol. Ther. 28, 431\u2013436 (2020).","journal-title":"Biomol. Ther."},{"key":"41712_CR50","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.ijcard.2016.08.233","volume":"223","author":"R Ghosh","year":"2016","unstructured":"Ghosh, R., Goswami, S. K., Feitoza, L. F. B. B., Hammock, B. & Gomes, A. V. Diclofenac induces proteasome and mitochondrial dysfunction in murine cardiomyocytes and hearts. Int. J. Cardiol. 223, 923\u2013935 (2016).","journal-title":"Int. J. Cardiol."},{"key":"41712_CR51","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/sj.cdd.4401436","volume":"11","author":"S Tsutsumi","year":"2004","unstructured":"Tsutsumi, S. et al. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death Differ. 11, 1009\u20131016 (2004).","journal-title":"Cell Death Differ."},{"key":"41712_CR52","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.pharmtox.38.1.97","volume":"38","author":"JR Vane","year":"1998","unstructured":"Vane, J. R., Bakhle, Y. S. & Botting, R. M. Cyclooxygenases 1 and 2. Annu. Rev. Pharmacol. Toxicol. 38, 97\u2013120 (1998).","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"41712_CR53","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.abb.2018.12.027","volume":"663","author":"A El Shatshat","year":"2019","unstructured":"El Shatshat, A., Pham, A. T. & Rao, P. P. N. Interactions of polyunsaturated fatty acids with amyloid peptides A\u03b240 and A\u03b242. Arch. Biochem. Biophys. 663, 34\u201343 (2019).","journal-title":"Arch. Biochem. Biophys."},{"key":"41712_CR54","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1038\/emboj.2010.143","volume":"29","author":"D Dormann","year":"2010","unstructured":"Dormann, D. et al. ALS-associated fused in sarcoma (FUS) mutations disrupt transportin-mediated nuclear import. EMBO J. 29, 2841\u20132857 (2010).","journal-title":"EMBO J."},{"key":"41712_CR55","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1091\/mbc.e04-08-0715","volume":"15","author":"N Gilks","year":"2004","unstructured":"Gilks, N. et al. Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol. Biol. Cell 15, 5383\u20135398 (2004).","journal-title":"Mol. Biol. Cell"},{"key":"41712_CR56","doi-asserted-by":"crossref","first-page":"110640","DOI":"10.1016\/j.colsurfb.2019.110640","volume":"186","author":"KP Prajapati","year":"2020","unstructured":"Prajapati, K. P. et al. Myricetin inhibits amyloid fibril formation of globular proteins by stabilizing the native structures. Coll. Surf. B Biointerfaces 186, 110640 (2020).","journal-title":"Coll. Surf. B Biointerfaces"},{"key":"41712_CR57","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/cbic.201000790","volume":"12","author":"AS Detoma","year":"2011","unstructured":"Detoma, A. S., Choi, J. S., Braymer, J. J. & Lim, M. H. Myricetin: A naturally occurring regulator of metal-induced amyloid-\u03b2 aggregation and neurotoxicity. ChemBioChem 12, 1198\u20131201 (2011).","journal-title":"ChemBioChem"},{"key":"41712_CR58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/braincomms\/fcaa109","volume":"2","author":"J Rivers-Auty","year":"2020","unstructured":"Rivers-Auty, J., Mather, A. E., Peters, R., Lawrence, C. B. & Brough, D. Anti-inflammatories in Alzheimer\u2019s disease\u2014potential therapy or spurious correlate?. Brain Commun. 2, 1\u201314 (2020).","journal-title":"Brain Commun."},{"key":"41712_CR59","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1002\/alz.12312","volume":"17","author":"K Madrasi","year":"2021","unstructured":"Madrasi, K. et al. Systematic in silico analysis of clinically tested drugs for reducing amyloid-beta plaque accumulation in Alzheimer\u2019s disease. Alzheimer\u2019s Dement 17, 1487\u20131498 (2021).","journal-title":"Alzheimer\u2019s Dement"},{"key":"41712_CR60","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.apsb.2021.08.030","volume":"12","author":"M Guo","year":"2022","unstructured":"Guo, M. et al. High-throughput screening for amyloid-\u03b2 binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC\u2212DAD-Q\/TOF-MS\/MS. Acta Pharm. Sin. B 12, 1723\u20131739 (2022).","journal-title":"Acta Pharm. Sin. B"},{"key":"41712_CR61","doi-asserted-by":"crossref","first-page":"E200","DOI":"10.1073\/pnas.1615613114","volume":"114","author":"J Habchi","year":"2017","unstructured":"Habchi, J. et al. Systematic development of small molecules to inhibit specific microscopic steps of A\u03b242 aggregation in Alzheimer\u2019s disease. Proc. Natl. Acad. Sci. U. S. A. 114, E200\u2013E208 (2017).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"41712_CR62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep23349","volume":"6","author":"A Espargar\u00f3","year":"2016","unstructured":"Espargar\u00f3, A., Medina, A., Di Pietro, O., Mu\u00f1oz-Torrero, D. & Sabate, R. Ultra rapid in vivo screening for anti-Alzheimer anti-amyloid drugs. Sci. Rep. 6, 1\u20138 (2016).","journal-title":"Sci. Rep."},{"key":"41712_CR63","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/biot.200600176","volume":"1","author":"M Artal-Sanz","year":"2006","unstructured":"Artal-Sanz, M., de Jong, L. & Tavernarakis, N. Caenorhabditis elegans: A versatile platform for drug discovery. Biotechnol. J. 1, 1405\u20131418 (2006).","journal-title":"Biotechnol. J."},{"key":"41712_CR64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1326-7-57","volume":"7","author":"G Mccoll","year":"2012","unstructured":"Mccoll, G. et al. Utility of an improved model of amyloid-beta (A\u03b21-42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer\u2019s disease. Mol. Neurodegener. 7, 1\u20139 (2012).","journal-title":"Mol. Neurodegener."},{"key":"41712_CR65","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s41573-022-00505-4","volume":"21","author":"DM Mitrea","year":"2022","unstructured":"Mitrea, D. M., Mittasch, M., Gomes, B. F., Klein, I. A. & Murcko, M. A. Modulating biomolecular condensates: A novel approach to drug discovery. Nat. Rev. Drug Discov. 21, 841\u2013862 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"41712_CR66","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3109\/13506129.2010.530081","volume":"17","author":"DJ Martin","year":"2010","unstructured":"Martin, D. J. & Ramirez-Alvarado, M. Comparison of amyloid fibril formation by two closely related immunoglobulin light chain variable domains. Amyloid 17, 129\u2013136 (2010).","journal-title":"Amyloid"},{"key":"41712_CR67","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.molcel.2011.12.012","volume":"45","author":"TE Audas","year":"2012","unstructured":"Audas, T. E., Jacob, M. D. & Lee, S. Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA. Mol. Cell 45, 147\u2013157 (2012).","journal-title":"Mol. Cell"},{"key":"41712_CR68","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ab.2010.02.001","volume":"400","author":"L Giehm","year":"2010","unstructured":"Giehm, L. & Otzen, D. E. Strategies to increase the reproducibility of protein fibrillization in plate reader assays. Anal. Biochem. 400, 270\u2013281 (2010).","journal-title":"Anal. Biochem."},{"key":"41712_CR69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21769\/BioProtoc.2941","volume":"8","author":"M W\u00f6rdehoff","year":"2018","unstructured":"W\u00f6rdehoff, M. & Hoyer, W. \u03b1-Synuclein aggregation monitored by thioflavin T fluorescence assay. Bio-Protoc. 8, 1\u201311 (2018).","journal-title":"Bio-Protoc."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-41712-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-41712-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-41712-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T12:17:03Z","timestamp":1700396223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-41712-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,2]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["41712"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-41712-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,2]]},"assertion":[{"value":"19 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14471"}}