{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:48:44Z","timestamp":1790736524622,"version":"4.1.0"},"reference-count":123,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"crossref","award":["24JRRA346"],"award-info":[{"award-number":["24JRRA346"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u201cCuiying Science and Technology Program\u201d of the Second Hospital of Lanzhou University","award":["CY2023-QN-B03"],"award-info":[{"award-number":["CY2023-QN-B03"]}]},{"name":"Foundation for International Medical Exchanges","award":["(23)0207"],"award-info":[{"award-number":["(23)0207"]}]},{"DOI":"10.13039\/501100017661","name":"China Health Promotion Foundation","doi-asserted-by":"publisher","award":["(23)1263"],"award-info":[{"award-number":["(23)1263"]}],"id":[{"id":"10.13039\/501100017661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurochem Res"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1007\/s11064-025-04448-1","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T04:48:19Z","timestamp":1749530899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["From RIPK1 to Necroptosis: Pathogenic Mechanisms in Neurodegenerative Diseases"],"prefix":"10.1007","volume":"50","author":[{"given":"Anjuan","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunli","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixing","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haile","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinliang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"issue":"8","key":"4448_CR1","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1038\/s12276-023-01078-x","volume":"55","author":"W Park","year":"2023","unstructured":"Park W, Wei S, Kim BS, Kim B, Bae SJ, Chae YC, Ryu D, Ha KT (2023) Diversity and complexity of cell death: a historical review. Exp Mol Med 55(8):1573\u20131594. https:\/\/doi.org\/10.1038\/s12276-023-01078-x","journal-title":"Exp Mol Med"},{"issue":"4","key":"4448_CR2","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","volume":"35","author":"S Elmore","year":"2007","unstructured":"Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495\u2013516. https:\/\/doi.org\/10.1080\/01926230701320337","journal-title":"Toxicol Pathol"},{"issue":"2","key":"4448_CR3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.cell.2023.11.044","volume":"187","author":"K Newton","year":"2024","unstructured":"Newton K, Strasser A, Kayagaki N, Dixit VM (2024) Cell death. Cell 187(2):235\u2013256. https:\/\/doi.org\/10.1016\/j.cell.2023.11.044","journal-title":"Cell"},{"issue":"5","key":"4448_CR4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.trecan.2023.02.001","volume":"9","author":"K H\u00e4nggi","year":"2023","unstructured":"H\u00e4nggi K, Ruffell B (2023) Cell death, therapeutics, and the immune response in cancer. Trends cancer 9(5):381\u2013396. https:\/\/doi.org\/10.1016\/j.trecan.2023.02.001","journal-title":"Trends cancer"},{"issue":"10","key":"4448_CR5","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/s41419-023-06154-8","volume":"14","author":"S Liu","year":"2023","unstructured":"Liu S, Yao S, Yang H, Liu S, Wang Y (2023) Autophagy: regulator of cell death. Cell Death Dis 14(10):648. https:\/\/doi.org\/10.1038\/s41419-023-06154-8","journal-title":"Cell Death Dis"},{"issue":"5","key":"4448_CR6","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","volume":"18","author":"D Bertheloot","year":"2021","unstructured":"Bertheloot D, Latz E, Franklin BS (2021) Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 18(5):1106\u20131121. https:\/\/doi.org\/10.1038\/s41423-020-00630-3","journal-title":"Cell Mol Immunol"},{"issue":"5","key":"4448_CR7","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41580-023-00689-6","volume":"25","author":"J Yuan","year":"2024","unstructured":"Yuan J, Ofengeim D (2024) A guide to cell death pathways. Nat Rev Mol Cell Biol 25(5):379\u2013395. https:\/\/doi.org\/10.1038\/s41580-023-00689-6","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"4448_CR8","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12974-018-1235-0","volume":"15","author":"YK Dhuriya","year":"2018","unstructured":"Dhuriya YK, Sharma D (2018) Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflamm 15(1):199. https:\/\/doi.org\/10.1186\/s12974-018-1235-0","journal-title":"J Neuroinflamm"},{"issue":"7628","key":"4448_CR9","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/539179a","volume":"539","author":"MT Heemels","year":"2016","unstructured":"Heemels MT (2016) Neurodegenerative diseases. Nature 539(7628):179. https:\/\/doi.org\/10.1038\/539179a","journal-title":"Nature"},{"key":"4448_CR10","doi-asserted-by":"publisher","unstructured":"Dugger BN, Dickson DW (2017) Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 9(7). https:\/\/doi.org\/10.1101\/cshperspect.a028035","DOI":"10.1101\/cshperspect.a028035"},{"key":"4448_CR11","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1146\/annurev-biochem-061516-045049","volume":"88","author":"J Vaquer-Alicea","year":"2019","unstructured":"Vaquer-Alicea J, Diamond MI (2019) Propagation of protein aggregation in neurodegenerative diseases. Annu Rev Biochem 88:785\u2013810. https:\/\/doi.org\/10.1146\/annurev-biochem-061516-045049","journal-title":"Annu Rev Biochem"},{"issue":"2","key":"4448_CR12","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s12035-014-9070-5","volume":"53","author":"Y Tang","year":"2016","unstructured":"Tang Y, Le W (2016) Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol 53(2):1181\u20131194. https:\/\/doi.org\/10.1007\/s12035-014-9070-5","journal-title":"Mol Neurobiol"},{"key":"4448_CR13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev-physiol-021113-170259","volume":"76","author":"DE Christofferson","year":"2014","unstructured":"Christofferson DE, Li Y, Yuan J (2014) Control of life-or-death decisions by RIP1 kinase. Annu Rev Physiol 76:129\u2013150. https:\/\/doi.org\/10.1146\/annurev-physiol-021113-170259","journal-title":"Annu Rev Physiol"},{"key":"4448_CR14","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.semcdb.2020.08.008","volume":"109","author":"DS Simpson","year":"2021","unstructured":"Simpson DS, Gabrielyan A, Feltham R (2021) RIPK1 ubiquitination: evidence, correlations and the undefined. Semin Cell Dev Biol 109:76\u201385. https:\/\/doi.org\/10.1016\/j.semcdb.2020.08.008","journal-title":"Semin Cell Dev Biol"},{"issue":"7712","key":"4448_CR15","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41586-018-0256-2","volume":"559","author":"K Heger","year":"2018","unstructured":"Heger K, Wickliffe KE, Ndoja A, Zhang J, Murthy A, Dugger DL, Maltzman A, de Sousa EMF, Hung J, Zeng Y, Verschueren E, Kirkpatrick DS, Vucic D, Lee WP, Roose-Girma M, Newman RJ, Warming S, Hsiao YC, K\u0151m\u0171ves LG, Webster JD, Newton K, Dixit VM (2018) OTULIN limits cell death and inflammation by deubiquitinating LUBAC. Nature 559(7712):120\u2013124. https:\/\/doi.org\/10.1038\/s41586-018-0256-2","journal-title":"Nature"},{"issue":"1","key":"4448_CR16","doi-asserted-by":"publisher","first-page":"6603","DOI":"10.1038\/s41467-022-34080-4","volume":"13","author":"H Tu","year":"2022","unstructured":"Tu H, Xiong W, Zhang J, Zhao X, Lin X (2022) Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation. Nat Commun 13(1):6603. https:\/\/doi.org\/10.1038\/s41467-022-34080-4","journal-title":"Nat Commun"},{"issue":"7778","key":"4448_CR17","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/s41586-019-1548-x","volume":"574","author":"K Newton","year":"2019","unstructured":"Newton K, Wickliffe KE, Dugger DL, Maltzman A, Roose-Girma M, Dohse M, K\u0151m\u0171ves L, Webster JD, Dixit VM (2019) Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis. Nature 574(7778):428\u2013431. https:\/\/doi.org\/10.1038\/s41586-019-1548-x","journal-title":"Nature"},{"key":"4448_CR18","doi-asserted-by":"publisher","unstructured":"Wu Q, Zou C (2022) Microglial dysfunction in neurodegenerative diseases via RIPK1 and ROS. Antioxid (Basel Switzerland) 11(11). https:\/\/doi.org\/10.3390\/antiox11112201","DOI":"10.3390\/antiox11112201"},{"key":"4448_CR19","doi-asserted-by":"publisher","unstructured":"Liang W, Qi W, Geng Y, Wang L, Zhao J, Zhu K, Wu G, Zhang Z, Pan H, Qian L, Yuan J (2021) Necroptosis activates UPR sensors without disrupting their binding with GRP78. Proc Natl Acad Sci USA 118(39). https:\/\/doi.org\/10.1073\/pnas.2110476118","DOI":"10.1073\/pnas.2110476118"},{"issue":"1","key":"4448_CR20","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","volume":"8","author":"X Chen","year":"2023","unstructured":"Chen X, Shi C, He M, Xiong S, Xia X (2023) Endoplasmic reticulum stress: molecular mechanism and therapeutic targets. Signal Transduct Target Therapy 8(1):352. https:\/\/doi.org\/10.1038\/s41392-023-01570-w","journal-title":"Signal Transduct Target Therapy"},{"issue":"12","key":"4448_CR21","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.4049\/jimmunol.1303380","volume":"192","author":"S McComb","year":"2014","unstructured":"McComb S, Shutinoski B, Thurston S, Cessford E, Kumar K, Sad S (2014) Cathepsins limit macrophage necroptosis through cleavage of Rip1 kinase. J Immunol (Baltimore Md: 1950) 192(12):5671\u20135678. https:\/\/doi.org\/10.4049\/jimmunol.1303380","journal-title":"J Immunol (Baltimore Md: 1950)"},{"issue":"1","key":"4448_CR22","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nrm.2017.83","volume":"19","author":"M Rape","year":"2018","unstructured":"Rape M (2018) Ubiquitylation at the crossroads of development and disease. Nat Rev Mol Cell Biol 19(1):59\u201370. https:\/\/doi.org\/10.1038\/nrm.2017.83","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9\u201310","key":"4448_CR23","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1007\/s10495-022-01755-8","volume":"27","author":"Y Chen","year":"2022","unstructured":"Chen Y, Ren W, Wang Q, He Y, Ma D, Cai Z (2022) The regulation of necroptosis by ubiquitylation. Apoptosis: Int J Program Cell Death 27(9\u201310):668\u2013684. https:\/\/doi.org\/10.1007\/s10495-022-01755-8","journal-title":"Apoptosis: Int J Program Cell Death"},{"issue":"7","key":"4448_CR24","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1038\/cdd.2017.46","volume":"24","author":"M Lork","year":"2017","unstructured":"Lork M, Verhelst K, Beyaert R (2017) CYLD, A20 and OTULIN deubiquitinases in NF-\u03baB signaling and cell death: so similar, yet so different. Cell Death Differ 24(7):1172\u20131183. https:\/\/doi.org\/10.1038\/cdd.2017.46","journal-title":"Cell Death Differ"},{"issue":"22","key":"4448_CR25","doi-asserted-by":"publisher","first-page":"e113614","DOI":"10.15252\/embj.2023113614","volume":"42","author":"F Schorn","year":"2023","unstructured":"Schorn F, Werthenbach JP, Hoffmann M, Daoud M, Stachelscheid J, Schiffmann LM, Hildebrandt X, Lyu SI, Peltzer N, Quaas A, Vucic D, Silke J, Pasparakis M, Kashkar H (2023) cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation. EMBO J 42(22):e113614. https:\/\/doi.org\/10.15252\/embj.2023113614","journal-title":"EMBO J"},{"issue":"7703","key":"4448_CR26","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41586-018-0064-8","volume":"557","author":"N Peltzer","year":"2018","unstructured":"Peltzer N, Darding M, Montinaro A, Draber P, Draberova H, Kupka S, Rieser E, Fisher A, Hutchinson C, Taraborrelli L, Hartwig T, Lafont E, Haas TL, Shimizu Y, B\u00f6iers C, Sarr A, Rickard J, Alvarez-Diaz S, Ashworth MT, Beal A, Enver T, Bertin J, Kaiser W, Strasser A, Silke J, Bouillet P, Walczak H (2018) LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis. Nature 557(7703):112\u2013117. https:\/\/doi.org\/10.1038\/s41586-018-0064-8","journal-title":"Nature"},{"issue":"9","key":"4448_CR27","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.15252\/embj.201695699","volume":"36","author":"E Lafont","year":"2017","unstructured":"Lafont E, Kantari-Mimoun C, Draber P, De Miguel D, Hartwig T, Reichert M, Kupka S, Shimizu Y, Taraborrelli L, Spit M, Sprick MR, Walczak H (2017) The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death. EMBO J 36(9):1147\u20131166. https:\/\/doi.org\/10.15252\/embj.201695699","journal-title":"EMBO J"},{"issue":"5","key":"4448_CR28","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.1074\/jbc.M407724200","volume":"280","author":"A Yamamoto","year":"2005","unstructured":"Yamamoto A, Friedlein A, Imai Y, Takahashi R, Kahle PJ, Haass C (2005) Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity. J Biol Chem 280(5):3390\u20133399. https:\/\/doi.org\/10.1074\/jbc.M407724200","journal-title":"J Biol Chem"},{"issue":"3","key":"4448_CR29","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ncb3314","volume":"18","author":"J Seo","year":"2016","unstructured":"Seo J, Lee EW, Sung H, Seong D, Dondelinger Y, Shin J, Jeong M, Lee HK, Kim JH, Han SY, Lee C, Seong JK, Vandenabeele P, Song J (2016) CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3. Nat Cell Biol 18(3):291\u2013302. https:\/\/doi.org\/10.1038\/ncb3314","journal-title":"Nat Cell Biol"},{"issue":"3","key":"4448_CR30","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nsmb.2970","volume":"22","author":"Y Sato","year":"2015","unstructured":"Sato Y, Goto E, Shibata Y, Kubota Y, Yamagata A, Goto-Ito S, Kubota K, Inoue J, Takekawa M, Tokunaga F, Fukai S (2015) Structures of CYLD USP with Met1- or Lys63-linked Diubiquitin reveal mechanisms for dual specificity. Nat Struct Mol Biol 22(3):222\u2013229. https:\/\/doi.org\/10.1038\/nsmb.2970","journal-title":"Nat Struct Mol Biol"},{"issue":"6","key":"4448_CR31","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1073\/pnas.1518163113","volume":"113","author":"J Zilberman-Rudenko","year":"2016","unstructured":"Zilberman-Rudenko J, Shawver LM, Wessel AW, Luo Y, Pelletier M, Tsai WL, Lee Y, Vonortas S, Cheng L, Ashwell JD, Orange JS, Siegel RM, Hanson EP (2016) Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-\u03baB activation and autoinflammatory disease. Proc Natl Acad Sci USA 113(6):1612\u20131617. https:\/\/doi.org\/10.1073\/pnas.1518163113","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"4448_CR32","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.devcel.2007.10.009","volume":"13","author":"SJS Simonson","year":"2007","unstructured":"Simonson SJS, Wu ZH, Miyamoto S (2007) CYLD: a DUB with many talents. Dev Cell 13(5):601\u2013603. https:\/\/doi.org\/10.1016\/j.devcel.2007.10.009","journal-title":"Dev Cell"},{"issue":"6","key":"4448_CR33","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/ni.3174","volume":"16","author":"P Gurung","year":"2015","unstructured":"Gurung P, Man SM, Kanneganti TD (2015) A20 is a regulator of necroptosis. Nat Immunol 16(6):596\u2013597. https:\/\/doi.org\/10.1038\/ni.3174","journal-title":"Nat Immunol"},{"issue":"1","key":"4448_CR34","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1038\/s41467-020-15466-8","volume":"11","author":"L Laurien","year":"2020","unstructured":"Laurien L, Nagata M, Sch\u00fcnke H, Delanghe T, Wiederstein JL, Kumari S, Schwarzer R, Corona T, Kr\u00fcger M, Bertrand MJM, Kondylis V, Pasparakis M (2020) Autophosphorylation at Serine 166 regulates RIP kinase 1-mediated cell death and inflammation. Nat Commun 11(1):1747. https:\/\/doi.org\/10.1038\/s41467-020-15466-8","journal-title":"Nat Commun"},{"key":"4448_CR35","doi-asserted-by":"publisher","first-page":"14329","DOI":"10.1038\/ncomms14329","volume":"8","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Su SS, Zhao S, Yang Z, Zhong CQ, Chen X, Cai Q, Yang ZH, Huang D, Wu R, Han J (2017) RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun 8:14329. https:\/\/doi.org\/10.1038\/ncomms14329","journal-title":"Nat Commun"},{"key":"4448_CR36","doi-asserted-by":"publisher","unstructured":"Du J, Wang Z (2024) Regulation of RIPK1 phosphorylation: implications for inflammation, cell death, and therapeutic interventions. Biomedicines 12(7). https:\/\/doi.org\/10.3390\/biomedicines12071525","DOI":"10.3390\/biomedicines12071525"},{"key":"4448_CR37","doi-asserted-by":"publisher","unstructured":"Gong CX, Liu F, Grundke-Iqbal I, Iqbal K (2006) Dysregulation of protein phosphorylation\/dephosphorylation in Alzheimer\u2019s disease: a therapeutic target. Journal of biomedicine & biotechnology 2006 (3):31825. https:\/\/doi.org\/10.1155\/jbb\/2006\/31825","DOI":"10.1155\/jbb\/2006\/31825"},{"issue":"23","key":"4448_CR38","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1111\/febs.14300","volume":"284","author":"S Kasai","year":"2017","unstructured":"Kasai S, Richardson MJE, Torii S, Yasumoto KI, Shima H, Igarashi K, Itoh K, Sogawa K, Murayama K (2017) Increase in proapoptotic activity of inhibitory PAS domain protein via phosphorylation by MK2. FEBS J 284(23):4115\u20134127. https:\/\/doi.org\/10.1111\/febs.14300","journal-title":"FEBS J"},{"issue":"6","key":"4448_CR39","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1016\/j.cell.2018.07.041","volume":"174","author":"D Xu","year":"2018","unstructured":"Xu D, Jin T, Zhu H, Chen H, Ofengeim D, Zou C, Mifflin L, Pan L, Amin P, Li W, Shan B, Naito MG, Meng H, Li Y, Pan H, Aron L, Adiconis X, Levin JZ, Yankner BA, Yuan J (2018) TBK1 suppresses RIPK1-Driven apoptosis and inflammation during development and in aging. Cell 174(6):1477\u20131491e1419. https:\/\/doi.org\/10.1016\/j.cell.2018.07.041","journal-title":"Cell"},{"issue":"12","key":"4448_CR40","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1038\/s41556-018-0229-6","volume":"20","author":"E Lafont","year":"2018","unstructured":"Lafont E, Draber P, Rieser E, Reichert M, Kupka S, de Miguel D, Draberova H, von M\u00e4ssenhausen A, Bhamra A, Henderson S, Wojdyla K, Chalk A, Surinova S, Linkermann A, Walczak H (2018) TBK1 and IKK\u03b5 prevent TNF-induced cell death by RIPK1 phosphorylation. Nat Cell Biol 20(12):1389\u20131399. https:\/\/doi.org\/10.1038\/s41556-018-0229-6","journal-title":"Nat Cell Biol"},{"issue":"1","key":"4448_CR41","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41467-017-00406-w","volume":"8","author":"J Geng","year":"2017","unstructured":"Geng J, Ito Y, Shi L, Amin P, Chu J, Ouchida AT, Mookhtiar AK, Zhao H, Xu D, Shan B, Najafov A, Gao G, Akira S, Yuan J (2017) Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat Commun 8(1):359. https:\/\/doi.org\/10.1038\/s41467-017-00406-w","journal-title":"Nat Commun"},{"issue":"13","key":"4448_CR42","doi-asserted-by":"publisher","first-page":"4181","DOI":"10.7150\/ijbs.85158","volume":"19","author":"J Zhang","year":"2023","unstructured":"Zhang J, Zhang R, Li W, Ma XC, Qiu F, Sun CP (2023) I\u03baB kinase \u03b2 (IKK\u03b2): structure, transduction mechanism, biological function, and discovery of its inhibitors. Int J Biol Sci 19(13):4181\u20134203. https:\/\/doi.org\/10.7150\/ijbs.85158","journal-title":"Int J Biol Sci"},{"key":"4448_CR43","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.cyto.2015.10.014","volume":"78","author":"CP Dillon","year":"2016","unstructured":"Dillon CP, Balachandran S (2016) StIKKing it to a death kinase: IKKs prevent TNF-\u03b1-induced cell death by phosphorylating RIPK1. Cytokine 78:47\u201350. https:\/\/doi.org\/10.1016\/j.cyto.2015.10.014","journal-title":"Cytokine"},{"issue":"5","key":"4448_CR44","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.molcel.2017.05.003","volume":"66","author":"I Jaco","year":"2017","unstructured":"Jaco I, Annibaldi A, Lalaoui N, Wilson R, Tenev T, Laurien L, Kim C, Jamal K, Wicky John S, Liccardi G, Chau D, Murphy JM, Brumatti G, Feltham R, Pasparakis M, Silke J, Meier P (2017) MK2 phosphorylates RIPK1 to prevent TNF-Induced cell death. Mol Cell 66(5):698\u2013710e695. https:\/\/doi.org\/10.1016\/j.molcel.2017.05.003","journal-title":"Mol Cell"},{"issue":"10","key":"4448_CR45","doi-asserted-by":"publisher","first-page":"5805","DOI":"10.1007\/s12035-023-03433-5","volume":"60","author":"G Sahoo","year":"2023","unstructured":"Sahoo G, Samal D, Khandayataray P, Murthy MK (2023) A review on caspases: key regulators of biological activities and apoptosis. Mol Neurobiol 60(10):5805\u20135837. https:\/\/doi.org\/10.1007\/s12035-023-03433-5","journal-title":"Mol Neurobiol"},{"issue":"19","key":"4448_CR46","doi-asserted-by":"publisher","first-page":"4246","DOI":"10.1111\/febs.15260","volume":"287","author":"P Smyth","year":"2020","unstructured":"Smyth P, Sessler T, Scott CJ, Longley DB (2020) FLIP(L): the pseudo-caspase. FEBS J 287(19):4246\u20134260. https:\/\/doi.org\/10.1111\/febs.15260","journal-title":"FEBS J"},{"issue":"7784","key":"4448_CR47","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41586-019-1752-8","volume":"575","author":"K Newton","year":"2019","unstructured":"Newton K, Wickliffe KE, Maltzman A, Dugger DL, Reja R, Zhang Y, Roose-Girma M, Modrusan Z, Sagolla MS, Webster JD, Dixit VM (2019) Activity of caspase-8 determines plasticity between cell death pathways. Nature 575(7784):679\u2013682. https:\/\/doi.org\/10.1038\/s41586-019-1752-8","journal-title":"Nature"},{"key":"4448_CR48","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2023.03.021","volume":"202","author":"P Wang","year":"2023","unstructured":"Wang P, Zheng SY, Jiang RL, Wu HD, Li YA, Lu JL, Xiong Y, Han B, Lin L (2023) Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma. Free Radic Biol Med 202:76\u201396. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2023.03.021","journal-title":"Free Radic Biol Med"},{"issue":"13","key":"4448_CR49","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.7150\/ijms.69992","volume":"19","author":"B Wang","year":"2022","unstructured":"Wang B, Fu J, Chai Y, Liu Y, Chen Y, Yin J, Pu Y, Chen C, Wang F, Liu Z, Zheng L, Chen M (2022) Accumulation of RIPK1 into mitochondria is requisite for oxidative stress-mediated necroptosis and proliferation in rat Schwann cells. Int J Med Sci 19(13):1965\u20131976. https:\/\/doi.org\/10.7150\/ijms.69992","journal-title":"Int J Med Sci"},{"key":"4448_CR50","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2018.01.024","volume":"117","author":"S Cadenas","year":"2018","unstructured":"Cadenas S (2018) ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic Biol Med 117:76\u201389. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2018.01.024","journal-title":"Free Radic Biol Med"},{"key":"4448_CR51","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","volume":"6","author":"DN Granger","year":"2015","unstructured":"Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524\u2013551. https:\/\/doi.org\/10.1016\/j.redox.2015.08.020","journal-title":"Redox Biol"},{"issue":"7","key":"4448_CR52","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/cdd.2017.65","volume":"24","author":"S Grootjans","year":"2017","unstructured":"Grootjans S, Vanden Berghe T, Vandenabeele P (2017) Initiation and execution mechanisms of necroptosis: an overview. Cell Death Differ 24(7):1184\u20131195. https:\/\/doi.org\/10.1038\/cdd.2017.65","journal-title":"Cell Death Differ"},{"issue":"3","key":"4448_CR53","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1038\/s41418-020-00722-7","volume":"28","author":"Y Meng","year":"2021","unstructured":"Meng Y, Sandow JJ, Czabotar PE, Murphy JM (2021) The regulation of necroptosis by post-translational modifications. Cell Death Differ 28(3):861\u2013883. https:\/\/doi.org\/10.1038\/s41418-020-00722-7","journal-title":"Cell Death Differ"},{"issue":"1","key":"4448_CR54","doi-asserted-by":"publisher","first-page":"6364","DOI":"10.1038\/s41467-020-19935-y","volume":"11","author":"X Li","year":"2020","unstructured":"Li X, Zhang M, Huang X, Liang W, Li G, Lu X, Li Y, Pan H, Shi L, Zhu H, Qian L, Shan B, Yuan J (2020) Ubiquitination of RIPK1 regulates its activation mediated by TNFR1 and TLRs signaling in distinct manners. Nat Commun 11(1):6364. https:\/\/doi.org\/10.1038\/s41467-020-19935-y","journal-title":"Nat Commun"},{"issue":"10","key":"4448_CR55","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1038\/s12276-022-00868-z","volume":"54","author":"MJ Morgan","year":"2022","unstructured":"Morgan MJ, Kim YS (2022) Roles of RIPK3 in necroptosis, cell signaling, and disease. Exp Mol Med 54(10):1695\u20131704. https:\/\/doi.org\/10.1038\/s12276-022-00868-z","journal-title":"Exp Mol Med"},{"issue":"1","key":"4448_CR56","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/febs.16255","volume":"290","author":"R Karlowitz","year":"2023","unstructured":"Karlowitz R, van Wijk SJL (2023) Surviving death: emerging concepts of RIPK3 and MLKL ubiquitination in the regulation of necroptosis. FEBS J 290(1):37\u201354. https:\/\/doi.org\/10.1111\/febs.16255","journal-title":"FEBS J"},{"issue":"1","key":"4448_CR57","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41418-023-01237-7","volume":"31","author":"S Liu","year":"2024","unstructured":"Liu S, Perez P, Sun X, Chen K, Fatirkhorani R, Mammadova J, Wang Z (2024) MLKL polymerization-induced lysosomal membrane permeabilization promotes necroptosis. Cell Death Differ 31(1):40\u201352. https:\/\/doi.org\/10.1038\/s41418-023-01237-7","journal-title":"Cell Death Differ"},{"key":"4448_CR58","doi-asserted-by":"publisher","unstructured":"Martinez-Osorio V, Abdelwahab Y, Ros U (2023) The many faces of MLKL, the executor of necroptosis. Int J Mol Sci 24(12). https:\/\/doi.org\/10.3390\/ijms241210108","DOI":"10.3390\/ijms241210108"},{"issue":"10","key":"4448_CR59","doi-asserted-by":"publisher","first-page":"4759","DOI":"10.7150\/thno.54072","volume":"11","author":"C Zhan","year":"2021","unstructured":"Zhan C, Huang M, Yang X, Hou J (2021) MLKL: functions beyond serving as the executioner of necroptosis. Theranostics 11(10):4759\u20134769. https:\/\/doi.org\/10.7150\/thno.54072","journal-title":"Theranostics"},{"issue":"8","key":"4448_CR60","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1007\/s11064-017-2249-1","volume":"42","author":"L Shao","year":"2017","unstructured":"Shao L, Yu S, Ji W, Li H, Gao Y (2017) The contribution of necroptosis in neurodegenerative diseases. Neurochem Res 42(8):2117\u20132126. https:\/\/doi.org\/10.1007\/s11064-017-2249-1","journal-title":"Neurochem Res"},{"issue":"1","key":"4448_CR61","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41583-018-0093-1","volume":"20","author":"J Yuan","year":"2019","unstructured":"Yuan J, Amin P, Ofengeim D (2019) Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat Rev Neurosci 20(1):19\u201333. https:\/\/doi.org\/10.1038\/s41583-018-0093-1","journal-title":"Nat Rev Neurosci"},{"issue":"10284","key":"4448_CR62","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/s0140-6736(20)32205-4","volume":"397","author":"P Scheltens","year":"2021","unstructured":"Scheltens P, De Strooper B, Kivipelto M, Holstege H, Ch\u00e9telat G, Teunissen CE, Cummings J, van der Flier WM (2021) Alzheimer\u2019s disease. Lancet (London England) 397(10284):1577\u20131590. https:\/\/doi.org\/10.1016\/s0140-6736(20)32205-4","journal-title":"Lancet (London England)"},{"key":"4448_CR63","doi-asserted-by":"publisher","unstructured":"Rostagno AA (2022) Pathogenesis of Alzheimer\u2019s Disease. Int J Mol Sci 24(1). https:\/\/doi.org\/10.3390\/ijms24010107","DOI":"10.3390\/ijms24010107"},{"key":"4448_CR64","doi-asserted-by":"publisher","unstructured":"Choi SB, Kwon S, Kim JH, Ahn NH, Lee JH, Yang SH (2023) The Molecular Mechanisms of Neuroinflammation in Alzheimer\u2019s Disease, the Consequence of Neural Cell Death. Int J Mol Sci 24(14). https:\/\/doi.org\/10.3390\/ijms241411757","DOI":"10.3390\/ijms241411757"},{"issue":"6663","key":"4448_CR65","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1126\/science.abp9556","volume":"381","author":"S Balusu","year":"2023","unstructured":"Balusu S, Horr\u00e9 K, Thrupp N, Craessaerts K, Snellinx A, Serneels L, T\u2019Syen D, Chrysidou I, Arranz AM, Sierksma A, Simr\u00e9n J, Karikari TK, Zetterberg H, Chen WT, Thal DR, Salta E, Fiers M, De Strooper B (2023) MEG3 activates necroptosis in human neuron xenografts modeling alzheimer\u2019s disease. Sci (New York NY) 381(6663):1176\u20131182. https:\/\/doi.org\/10.1126\/science.abp9556","journal-title":"Sci (New York NY)"},{"key":"4448_CR66","doi-asserted-by":"publisher","unstructured":"Rajesh Y, Kanneganti TD (2022) Innate Immune Cell Death in Neuroinflammation and Alzheimer\u2019s Disease. Cells 11(12). https:\/\/doi.org\/10.3390\/cells11121885","DOI":"10.3390\/cells11121885"},{"issue":"1","key":"4448_CR67","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s12017-024-08815-z","volume":"27","author":"X Zhuang","year":"2024","unstructured":"Zhuang X, Lin J, Song Y, Ban R, Zhao X, Xia Z, Wang Z, Zhang G (2024) The interplay between accumulation of Amyloid-Beta and Tau proteins, panoptosis, and inflammation in alzheimer\u2019s disease. Neuromol Med 27(1):2. https:\/\/doi.org\/10.1007\/s12017-024-08815-z","journal-title":"Neuromol Med"},{"issue":"1","key":"4448_CR68","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1186\/s12974-022-02613-9","volume":"19","author":"Y Li","year":"2022","unstructured":"Li Y, Xia X, Wang Y, Zheng JC (2022) Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of alzheimer\u2019s disease. J Neuroinflamm 19(1):248. https:\/\/doi.org\/10.1186\/s12974-022-02613-9","journal-title":"J Neuroinflamm"},{"issue":"41","key":"4448_CR69","doi-asserted-by":"publisher","first-page":"10813","DOI":"10.1073\/pnas.1715241114","volume":"114","author":"DC Rubinsztein","year":"2017","unstructured":"Rubinsztein DC (2017) RIPK1 promotes inflammation and \u03b2-amyloid accumulation in alzheimer\u2019s disease. Proc Natl Acad Sci U S A 114(41):10813\u201310814. https:\/\/doi.org\/10.1073\/pnas.1715241114","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"4448_CR70","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41422-021-00582-x","volume":"32","author":"K Pang","year":"2022","unstructured":"Pang K, Jiang R, Zhang W, Yang Z, Li LL, Shimozawa M, Tambaro S, Mayer J, Zhang B, Li M, Wang J, Liu H, Yang A, Chen X, Liu J, Winblad B, Han H, Jiang T, Wang W, Nilsson P, Guo W, Lu B (2022) An app knock-in rat model for alzheimer\u2019s disease exhibiting A\u03b2 and Tau pathologies, neuronal death and cognitive impairments. Cell Res 32(2):157\u2013175. https:\/\/doi.org\/10.1038\/s41422-021-00582-x","journal-title":"Cell Res"},{"key":"4448_CR71","doi-asserted-by":"publisher","first-page":"1530809","DOI":"10.3389\/fnins.2024.1530809","volume":"18","author":"I Silva-Llanes","year":"2025","unstructured":"Silva-Llanes I, Madruga E, Mart\u00ednez A, Lastres-Becker I (2025) RIPK1 expression and Inhibition in tauopathies: implications for neuroinflammation and neuroprotection. Front Neurosci 18:1530809. https:\/\/doi.org\/10.3389\/fnins.2024.1530809","journal-title":"Front Neurosci"},{"issue":"1","key":"4448_CR72","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s00401-024-02747-5","volume":"147","author":"S Balusu","year":"2024","unstructured":"Balusu S, De Strooper B (2024) The necroptosis cell death pathway drives neurodegeneration in alzheimer\u2019s disease. Acta Neuropathol 147(1):96. https:\/\/doi.org\/10.1007\/s00401-024-02747-5","journal-title":"Acta Neuropathol"},{"issue":"1","key":"4448_CR73","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s12974-022-02567-y","volume":"19","author":"Y Dong","year":"2022","unstructured":"Dong Y, Yu H, Li X, Bian K, Zheng Y, Dai M, Feng X, Sun Y, He Y, Yu B, Zhang H, Wu J, Yu X, Wu H, Kong W (2022) Hyperphosphorylated Tau mediates neuronal death by inducing necroptosis and inflammation in alzheimer\u2019s disease. J Neuroinflamm 19(1):205. https:\/\/doi.org\/10.1186\/s12974-022-02567-y","journal-title":"J Neuroinflamm"},{"issue":"1","key":"4448_CR74","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1186\/s12974-021-02327-4","volume":"18","author":"LL Cao","year":"2021","unstructured":"Cao LL, Guan PP, Zhang SQ, Yang Y, Huang XS, Wang P (2021) Downregulating expression of OPTN elevates neuroinflammation via AIM2 inflammasome- and RIPK1-activating mechanisms in APP\/PS1 Transgenic mice. J Neuroinflamm 18(1):281. https:\/\/doi.org\/10.1186\/s12974-021-02327-4","journal-title":"J Neuroinflamm"},{"key":"4448_CR75","doi-asserted-by":"publisher","first-page":"102575","DOI":"10.1016\/j.conb.2022.102575","volume":"75","author":"A Mangalmurti","year":"2022","unstructured":"Mangalmurti A, Lukens JR (2022) How neurons die in alzheimer\u2019s disease: implications for neuroinflammation. Curr Opin Neurobiol 75:102575. https:\/\/doi.org\/10.1016\/j.conb.2022.102575","journal-title":"Curr Opin Neurobiol"},{"issue":"10291","key":"4448_CR76","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/s0140-6736(21)00218-x","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem BR, Okun MS, Klein C (2021) Parkinson\u2019s disease. Lancet (London England) 397(10291):2284\u20132303. https:\/\/doi.org\/10.1016\/s0140-6736(21)00218-x","journal-title":"Lancet (London England)"},{"key":"4448_CR77","doi-asserted-by":"publisher","unstructured":"Pajares M, A IR, Manda G, Bosc\u00e1 L, Cuadrado A (2020) Inflammation in Parkinson\u2019s Disease: Mechanisms and Therapeutic Implications. Cells 9(7). https:\/\/doi.org\/10.3390\/cells9071687","DOI":"10.3390\/cells9071687"},{"key":"4448_CR78","doi-asserted-by":"publisher","first-page":"101263","DOI":"10.1016\/j.arr.2021.101263","volume":"67","author":"PA Dion\u00edsio","year":"2021","unstructured":"Dion\u00edsio PA, Amaral JD, Rodrigues CMP (2021) Oxidative stress and regulated cell death in parkinson\u2019s disease. Ageing Res Rev 67:101263. https:\/\/doi.org\/10.1016\/j.arr.2021.101263","journal-title":"Ageing Res Rev"},{"key":"4448_CR79","doi-asserted-by":"publisher","first-page":"1567445","DOI":"10.3389\/fnins.2025.1567445","volume":"19","author":"H Xiang","year":"2025","unstructured":"Xiang H (2025) The interplay between \u03b1-synuclein aggregation and necroptosis in parkinson\u2019s disease: a Spatiotemporal perspective. Front NeuroSci 19:1567445. https:\/\/doi.org\/10.3389\/fnins.2025.1567445","journal-title":"Front NeuroSci"},{"issue":"8","key":"4448_CR80","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41419-019-1809-5","volume":"10","author":"YB Hu","year":"2019","unstructured":"Hu YB, Zhang YF, Wang H, Ren RJ, Cui HL, Huang WY, Cheng Q, Chen HZ, Wang G (2019) miR-425 deficiency promotes necroptosis and dopaminergic neurodegeneration in parkinson\u2019s disease. Cell Death Dis 10(8):589. https:\/\/doi.org\/10.1038\/s41419-019-1809-5","journal-title":"Cell Death Dis"},{"issue":"8","key":"4448_CR81","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1016\/j.celrep.2018.01.089","volume":"22","author":"A Iannielli","year":"2018","unstructured":"Iannielli A, Bido S, Folladori L, Segnali A, Cancellieri C, Maresca A, Massimino L, Rubio A, Morabito G, Caporali L, Tagliavini F, Musumeci O, Gregato G, Bezard E, Carelli V, Tiranti V, Broccoli V (2018) Pharmacological Inhibition of necroptosis protects from dopaminergic neuronal cell death in parkinson\u2019s disease models. Cell Rep 22(8):2066\u20132079. https:\/\/doi.org\/10.1016\/j.celrep.2018.01.089","journal-title":"Cell Rep"},{"issue":"4","key":"4448_CR82","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/s41418-019-0408-4","volume":"27","author":"M O\u00f1ate","year":"2020","unstructured":"O\u00f1ate M, Catenaccio A, Salvadores N, Saquel C, Martinez A, Moreno-Gonzalez I, Gamez N, Soto P, Soto C, Hetz C, Court FA (2020) The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease. Cell Death Differ 27(4):1169\u20131185. https:\/\/doi.org\/10.1038\/s41418-019-0408-4","journal-title":"Cell Death Differ"},{"issue":"10360","key":"4448_CR83","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/s0140-6736(22)01272-7","volume":"400","author":"EL Feldman","year":"2022","unstructured":"Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, Sobue G (2022) Amyotrophic lateral sclerosis. Lancet (London England) 400(10360):1363\u20131380. https:\/\/doi.org\/10.1016\/s0140-6736(22)01272-7","journal-title":"Lancet (London England)"},{"key":"4448_CR84","doi-asserted-by":"publisher","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","volume":"3","author":"O Hardiman","year":"2017","unstructured":"Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH (2017) Amyotrophic lateral sclerosis. Nat Reviews Disease Primers 3:17071. https:\/\/doi.org\/10.1038\/nrdp.2017.71","journal-title":"Nat Reviews Disease Primers"},{"issue":"5","key":"4448_CR85","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/s1474-4422(21)00465-8","volume":"21","author":"SA Goutman","year":"2022","unstructured":"Goutman SA, Hardiman O, Al-Chalabi A, Chi\u00f3 A, Savelieff MG, Kiernan MC, Feldman EL (2022) Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis. Lancet Neurol 21(5):480\u2013493. https:\/\/doi.org\/10.1016\/s1474-4422(21)00465-8","journal-title":"Lancet Neurol"},{"key":"4448_CR86","doi-asserted-by":"publisher","unstructured":"Morrice JR, Gregory-Evans CY, Shaw CA (2017) Necroptosis in amyotrophic lateral sclerosis and other neurological disorders. Biochimica et biophysica acta molecular basis of disease 1863. 2347\u2013353. https:\/\/doi.org\/10.1016\/j.bbadis.2016.11.025","DOI":"10.1016\/j.bbadis.2016.11.025"},{"issue":"20","key":"4448_CR87","doi-asserted-by":"publisher","first-page":"R932","DOI":"10.1016\/j.cub.2016.08.052","volume":"26","author":"K Politi","year":"2016","unstructured":"Politi K, Przedborski S (2016) Axonal degeneration: RIPK1 multitasking in ALS. Curr Biology: CB 26(20):R932\u2013r934. https:\/\/doi.org\/10.1016\/j.cub.2016.08.052","journal-title":"Curr Biology: CB"},{"issue":"1","key":"4448_CR88","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41420-021-00458-4","volume":"7","author":"M Chevin","year":"2021","unstructured":"Chevin M, S\u00e9bire G (2021) Necroptosis in ALS: a hot topic in-progress. Cell Death Discovery 7(1):79. https:\/\/doi.org\/10.1038\/s41420-021-00458-4","journal-title":"Cell Death Discovery"},{"key":"4448_CR89","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pneurobio.2017.04.005","volume":"154","author":"A Markovinovic","year":"2017","unstructured":"Markovinovic A, Cimbro R, Ljutic T, Kriz J, Rogelj B, Munitic I (2017) Optineurin in amyotrophic lateral sclerosis: multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms. Prog Neurobiol 154:1\u201320. https:\/\/doi.org\/10.1016\/j.pneurobio.2017.04.005","journal-title":"Prog Neurobiol"},{"key":"4448_CR90","doi-asserted-by":"publisher","unstructured":"Ito, Y., Ofengeim, D., Najafov, A., Das, S., Saberi, S., Li, Y., Hitomi, J., Zhu,H., Chen, H., Mayo, L., Geng, J., Amin, P., DeWitt, J. P., Mookhtiar, A. K., Florez,M., Ouchida, A. T., Fan, J. B., Pasparakis, M., Kelliher, M. A., Ravits, J.,\u2026 Yuan,J. (2016) RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science (New York, N.Y.) 353(6299): 603\u2013608.https:\/\/doi.org\/10.1126\/science.aaf6803","DOI":"10.1126\/science.aaf6803"},{"issue":"6","key":"4448_CR91","doi-asserted-by":"publisher","first-page":"e2905","DOI":"10.1038\/cddis.2017.286","volume":"8","author":"S Zhang","year":"2017","unstructured":"Zhang S, Tang MB, Luo HY, Shi CH, Xu YM (2017) Necroptosis in neurodegenerative diseases: a potential therapeutic target. Cell Death Dis 8(6):e2905. https:\/\/doi.org\/10.1038\/cddis.2017.286","journal-title":"Cell Death Dis"},{"issue":"6299","key":"4448_CR92","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1126\/science.aaf6803","volume":"353","author":"Y Ito","year":"2016","unstructured":"Ito Y, Ofengeim D, Najafov A, Das S, Saberi S, Li Y, Hitomi J, Zhu H, Chen H, Mayo L, Geng J, Amin P, DeWitt JP, Mookhtiar AK, Florez M, Ouchida AT, Fan JB, Pasparakis M, Kelliher MA, Ravits J, Yuan J (2016) RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Sci (New York NY) 353(6299):603\u2013608. https:\/\/doi.org\/10.1126\/science.aaf6803","journal-title":"Sci (New York NY)"},{"issue":"1","key":"4448_CR93","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41420-024-02055-7","volume":"10","author":"B N\u00f3gr\u00e1di","year":"2024","unstructured":"N\u00f3gr\u00e1di B, N\u00f3gr\u00e1di-Halmi D, Erd\u00e9lyi-Furka B, K\u00e1d\u00e1r Z, Csont T, G\u00e1sp\u00e1r R (2024) Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation. Cell Death Discovery 10(1):291. https:\/\/doi.org\/10.1038\/s41420-024-02055-7","journal-title":"Cell Death Discovery"},{"issue":"11","key":"4448_CR94","doi-asserted-by":"publisher","first-page":"2878","DOI":"10.1007\/s00415-019-09541-4","volume":"266","author":"A Khellaf","year":"2019","unstructured":"Khellaf A, Khan DZ, Helmy A (2019) Recent advances in traumatic brain injury. J Neurol 266(11):2878\u20132889. https:\/\/doi.org\/10.1007\/s00415-019-09541-4","journal-title":"J Neurol"},{"issue":"3","key":"4448_CR95","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/s1474-4422(18)30469-1","volume":"18","author":"JY Jiang","year":"2019","unstructured":"Jiang JY, Gao GY, Feng JF, Mao Q, Chen LG, Yang XF, Liu JF, Wang YH, Qiu BH, Huang XJ (2019) Traumatic brain injury in China. Lancet Neurol 18(3):286\u2013295. https:\/\/doi.org\/10.1016\/s1474-4422(18)30469-1","journal-title":"Lancet Neurol"},{"issue":"8","key":"4448_CR96","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.2174\/1570159x15666170613083606","volume":"16","author":"P Kaur","year":"2018","unstructured":"Kaur P, Sharma S (2018) Recent advances in pathophysiology of traumatic brain injury. Curr Neuropharmacol 16(8):1224\u20131238. https:\/\/doi.org\/10.2174\/1570159x15666170613083606","journal-title":"Curr Neuropharmacol"},{"issue":"5","key":"4448_CR97","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","volume":"91","author":"BL Brett","year":"2022","unstructured":"Brett BL, Gardner RC, Godbout J, Dams-O\u2019Connor K, Keene CD (2022) Traumatic brain injury and risk of neurodegenerative disorder. Biol Psychiatry 91(5):498\u2013507. https:\/\/doi.org\/10.1016\/j.biopsych.2021.05.025","journal-title":"Biol Psychiatry"},{"issue":"4","key":"4448_CR98","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/bph.13125","volume":"173","author":"IP Karve","year":"2016","unstructured":"Karve IP, Taylor JM, Crack PJ (2016) The contribution of astrocytes and microglia to traumatic brain injury. Br J Pharmacol 173(4):692\u2013702. https:\/\/doi.org\/10.1111\/bph.13125","journal-title":"Br J Pharmacol"},{"issue":"2","key":"4448_CR99","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/BF00219219","volume":"244","author":"L Cieciura","year":"1986","unstructured":"Cieciura L, Rydzy\u0144ski K, Pieta P, Klimek I (1986) Freeze-fracture studies on mitochondrial membranes of spermatocytes. Cell Tissue Res 244(2):437\u2013441. https:\/\/doi.org\/10.1007\/BF00219219","journal-title":"Cell Tissue Res"},{"key":"4448_CR100","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jare.2021.12.002","volume":"40","author":"X Hu","year":"2022","unstructured":"Hu X, Xu Y, Zhang H, Li Y, Wang X, Xu C, Ni W, Zhou K (2022) Role of necroptosis in traumatic brain and spinal cord injuries. J Adv Res 40:125\u2013134. https:\/\/doi.org\/10.1016\/j.jare.2021.12.002","journal-title":"J Adv Res"},{"issue":"1","key":"4448_CR101","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s40478-021-01236-0","volume":"9","author":"AC Wehn","year":"2021","unstructured":"Wehn AC, Khalin I, Duering M, Hellal F, Culmsee C, Vandenabeele P, Plesnila N, Terpolilli NA (2021) RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury. Acta Neuropathol Commun 9(1):138. https:\/\/doi.org\/10.1186\/s40478-021-01236-0","journal-title":"Acta Neuropathol Commun"},{"key":"4448_CR102","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3389\/fnmol.2019.00222","volume":"12","author":"Z Bao","year":"2019","unstructured":"Bao Z, Fan L, Zhao L, Xu X, Liu Y, Chao H, Liu N, You Y, Liu Y, Wang X, Ji J (2019) Silencing of A20 aggravates neuronal death and inflammation after traumatic brain injury: A potential trigger of necroptosis. Front Mol Neurosci 12:222. https:\/\/doi.org\/10.3389\/fnmol.2019.00222","journal-title":"Front Mol Neurosci"},{"issue":"8","key":"4448_CR103","doi-asserted-by":"publisher","first-page":"e37297","DOI":"10.1097\/md.0000000000037297","volume":"103","author":"M Haki","year":"2024","unstructured":"Haki M, Al-Biati HA, Al-Tameemi ZS, Ali IS, Al-Hussaniy HA (2024) Review of multiple sclerosis: epidemiology, etiology, pathophysiology, and treatment. Medicine 103(8):e37297. https:\/\/doi.org\/10.1097\/md.0000000000037297","journal-title":"Medicine"},{"issue":"2","key":"4448_CR104","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.molmed.2018.11.005","volume":"25","author":"S Voet","year":"2019","unstructured":"Voet S, Prinz M, van Loo G (2019) Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends Mol Med 25(2):112\u2013123. https:\/\/doi.org\/10.1016\/j.molmed.2018.11.005","journal-title":"Trends Mol Med"},{"issue":"7","key":"4448_CR105","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1002\/glia.24148","volume":"70","author":"MK Sen","year":"2022","unstructured":"Sen MK, Mahns DA, Coorssen JR, Shortland PJ (2022) The roles of microglia and astrocytes in phagocytosis and myelination: insights from the Cuprizone model of multiple sclerosis. Glia 70(7):1215\u20131250. https:\/\/doi.org\/10.1002\/glia.24148","journal-title":"Glia"},{"issue":"1","key":"4448_CR106","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s40478-020-00938-1","volume":"8","author":"RE James","year":"2020","unstructured":"James RE, Schalks R, Browne E, Eleftheriadou I, Munoz CP, Mazarakis ND, Reynolds R (2020) Persistent elevation of intrathecal pro-inflammatory cytokines leads to multiple sclerosis-like cortical demyelination and neurodegeneration. Acta Neuropathol Commun 8(1):66. https:\/\/doi.org\/10.1186\/s40478-020-00938-1","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"4448_CR107","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13024-022-00538-8","volume":"17","author":"M Zirngibl","year":"2022","unstructured":"Zirngibl M, Assinck P, Sizov A, Caprariello AV, Plemel JR (2022) Oligodendrocyte death and Myelin loss in the Cuprizone model: an updated overview of the intrinsic and extrinsic causes of Cuprizone demyelination. Mol Neurodegeneration 17(1):34. https:\/\/doi.org\/10.1186\/s13024-022-00538-8","journal-title":"Mol Neurodegeneration"},{"issue":"6","key":"4448_CR108","doi-asserted-by":"publisher","first-page":"109112","DOI":"10.1016\/j.celrep.2021.109112","volume":"35","author":"M Zelic","year":"2021","unstructured":"Zelic M, Pontarelli F, Woodworth L, Zhu C, Mahan A, Ren Y, LaMorte M, Gruber R, Keane A, Loring P, Guo L, Xia TH, Zhang B, Orning P, Lien E, Degterev A, Hammond T, Ofengeim D (2021) RIPK1 activation mediates neuroinflammation and disease progression in multiple sclerosis. Cell Rep 35(6):109112. https:\/\/doi.org\/10.1016\/j.celrep.2021.109112","journal-title":"Cell Rep"},{"issue":"2","key":"4448_CR109","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.cyto.2015.06.004","volume":"76","author":"S Dhib-Jalbut","year":"2015","unstructured":"Dhib-Jalbut S, Kalvakolanu DV (2015) Microglia and necroptosis: the culprits of neuronal cell death in multiple sclerosis. Cytokine 76(2):583\u2013584. https:\/\/doi.org\/10.1016\/j.cyto.2015.06.004","journal-title":"Cytokine"},{"issue":"8","key":"4448_CR110","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-020-0071-y","volume":"19","author":"L Mifflin","year":"2020","unstructured":"Mifflin L, Ofengeim D, Yuan J (2020) Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat Rev Drug Discovery 19(8):553\u2013571. https:\/\/doi.org\/10.1038\/s41573-020-0071-y","journal-title":"Nat Rev Drug Discovery"},{"issue":"2","key":"4448_CR111","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nchembio711","volume":"1","author":"A Degterev","year":"2005","unstructured":"Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1(2):112\u2013119. https:\/\/doi.org\/10.1038\/nchembio711","journal-title":"Nat Chem Biol"},{"key":"4448_CR112","doi-asserted-by":"publisher","first-page":"105297","DOI":"10.1016\/j.phrs.2020.105297","volume":"163","author":"L Cao","year":"2021","unstructured":"Cao L, Mu W (2021) Necrostatin-1 and necroptosis inhibition: pathophysiology and therapeutic implications. Pharmacol Res 163:105297. https:\/\/doi.org\/10.1016\/j.phrs.2020.105297","journal-title":"Pharmacol Res"},{"key":"4448_CR113","doi-asserted-by":"publisher","first-page":"1408364","DOI":"10.3389\/fncel.2024.1408364","volume":"18","author":"KQ Chen","year":"2024","unstructured":"Chen KQ, Wang SZ, Lei HB, Liu X (2024) Necrostatin-1: a promising compound for neurological disorders. Front Cell Neurosci 18:1408364. https:\/\/doi.org\/10.3389\/fncel.2024.1408364","journal-title":"Front Cell Neurosci"},{"issue":"11","key":"4448_CR114","doi-asserted-by":"publisher","first-page":"e437","DOI":"10.1038\/cddis.2012.176","volume":"3","author":"N Takahashi","year":"2012","unstructured":"Takahashi N, Duprez L, Grootjans S, Cauwels A, Nerinckx W, DuHadaway JB, Goossens V, Roelandt R, Van Hauwermeiren F, Libert C, Declercq W, Callewaert N, Prendergast GC, Degterev A, Yuan J, Vandenabeele P (2012) Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis 3(11):e437. https:\/\/doi.org\/10.1038\/cddis.2012.176","journal-title":"Cell Death Dis"},{"key":"4448_CR115","doi-asserted-by":"publisher","first-page":"115380","DOI":"10.1016\/j.biopha.2023.115380","volume":"166","author":"J Zhang","year":"2023","unstructured":"Zhang J, Cao J, Qian J, Gu X, Zhang W, Chen X (2023) Regulatory mechanism of camkii \u03b4 mediated by RIPK3 on myocardial fibrosis and reversal effects of RIPK3 inhibitor GSK\u2019872. Biomed pharmacotherapy = Biomedecine Pharmacotherapie 166:115380. https:\/\/doi.org\/10.1016\/j.biopha.2023.115380","journal-title":"Biomed pharmacotherapy = Biomedecine Pharmacotherapie"},{"key":"4448_CR116","doi-asserted-by":"publisher","first-page":"e136","DOI":"10.1016\/j.wneu.2024.04.051","volume":"187","author":"Y Min","year":"2024","unstructured":"Min Y, Yu ZQ (2024) GSK\u2019872 improves prognosis of traumatic brain injury by switching Receptor-Interacting Serine\/Threonine-Protein kinase 3-dependent necroptosis to Cysteinyl aspartate specific Proteinase-8-Dependent apoptosis. World Neurosurg 187:e136\u2013e147. https:\/\/doi.org\/10.1016\/j.wneu.2024.04.051","journal-title":"World Neurosurg"},{"issue":"1","key":"4448_CR117","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s11095-021-03124-7","volume":"39","author":"D Tompson","year":"2022","unstructured":"Tompson D, Whitaker M, Pan R, Johnson G, Fuller T, Zann V, McKenzie L, Abbott-Banner K, Hawkins S, Powell M (2022) Development of a Once-Daily Modified-Release formulation for the short Half-Life RIPK1 inhibitor GSK2982772 using diffcore technology. Pharm Res 39(1):153\u2013165. https:\/\/doi.org\/10.1007\/s11095-021-03124-7","journal-title":"Pharm Res"},{"issue":"7","key":"4448_CR118","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1007\/s11095-021-03059-z","volume":"38","author":"DJ Tompson","year":"2021","unstructured":"Tompson DJ, Whitaker M, Pan R, Johnson G, Fuller T, McKenzie L, Zann V, Powell M, Abbott-Banner K, Hawkins S (2021) Development of a prototype, Once-Daily, Modified-Release formulation for the short Half-Life RIPK1 inhibitor GSK2982772. Pharm Res 38(7):1235\u20131245. https:\/\/doi.org\/10.1007\/s11095-021-03059-z","journal-title":"Pharm Res"},{"issue":"22","key":"4448_CR119","doi-asserted-by":"publisher","first-page":"14971","DOI":"10.1021\/acs.jmedchem.2c01518","volume":"65","author":"K Shi","year":"2022","unstructured":"Shi K, Zhang J, Zhou E, Wang J, Wang Y (2022) Small-Molecule Receptor-Interacting protein 1 (RIP1) inhibitors as therapeutic agents for multifaceted diseases: current medicinal chemistry insights and emerging opportunities. J Med Chem 65(22):14971\u201314999. https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01518","journal-title":"J Med Chem"},{"issue":"8","key":"4448_CR120","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1111\/cts.13317","volume":"15","author":"M Vissers","year":"2022","unstructured":"Vissers M, Heuberger J, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, Harris J, Tsai RM, Cruz-Herranz A, Huang F, Tong V, Erickson R, Zhu Y, Scearce-Levie K, Hsiao-Nakamoto J, Tang X, Chang M, Fox BM, Estrada AA, Pomponio RJ, Alonso-Alonso M, Zilberstein M, Atassi N, Troyer MD, Ho C (2022) Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: randomized, placebo-controlled, double-blind phase i\/ib studies in healthy subjects and patients. Clin Transl Sci 15(8):2010\u20132023. https:\/\/doi.org\/10.1111\/cts.13317","journal-title":"Clin Transl Sci"},{"issue":"1","key":"4448_CR121","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41420-022-00929-2","volume":"8","author":"XR Ma","year":"2022","unstructured":"Ma XR, Yang SY, Zheng SS, Yan HH, Gu HM, Wang F, Wu Y, Dong ZJ, Wang DX, Wang Y, Meng X, Sun J, Xia HG, Zhao JW (2022) Inhibition of RIPK1 by ZJU-37 promotes oligodendrocyte progenitor proliferation and remyelination via NF-\u03baB pathway. Cell Death Discovery 8(1):147. https:\/\/doi.org\/10.1038\/s41420-022-00929-2","journal-title":"Cell Death Discovery"},{"issue":"1\u20132","key":"4448_CR122","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s10495-023-01905-6","volume":"29","author":"Y Zhou","year":"2024","unstructured":"Zhou Y, Cai Z, Zhai Y, Yu J, He Q, He Y, Jitkaew S, Cai Z (2024) Necroptosis inhibitors: mechanisms of action and therapeutic potential. Apoptosis: Int J Program Cell Death 29(1\u20132):22\u201344. https:\/\/doi.org\/10.1007\/s10495-023-01905-6","journal-title":"Apoptosis: Int J Program Cell Death"},{"issue":"4","key":"4448_CR123","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1021\/acs.jmedchem.9b01317","volume":"63","author":"C Zhuang","year":"2020","unstructured":"Zhuang C, Chen F (2020) Small-Molecule inhibitors of necroptosis: current status and perspectives. J Med Chem 63(4):1490\u20131510. https:\/\/doi.org\/10.1021\/acs.jmedchem.9b01317","journal-title":"J Med Chem"}],"container-title":["Neurochemical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04448-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11064-025-04448-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04448-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T12:43:31Z","timestamp":1750682611000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11064-025-04448-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":123,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["4448"],"URL":"https:\/\/doi.org\/10.1007\/s11064-025-04448-1","relation":{},"ISSN":["0364-3190","1573-6903"],"issn-type":[{"value":"0364-3190","type":"print"},{"value":"1573-6903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"11 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"194"}}