{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:49:24Z","timestamp":1790344164049,"version":"4.1.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2023,11]]},"DOI":"10.1007\/s12035-023-03495-5","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T08:03:23Z","timestamp":1689926603000},"page":"6731-6747","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genome-wide CRISPR\u2013Cas9 Knockout Screening Reveals a TSPAN3-mediated Endo-lysosome Pathway Regulating the Degradation of \u03b1-Synuclein Oligomers"],"prefix":"10.1007","volume":"60","author":[{"given":"JunJian","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0730-1095","authenticated-orcid":false,"given":"Jieqiong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"issue":"8","key":"3495_CR1","doi-asserted-by":"publisher","first-page":"2804","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988","volume":"8","author":"L Maroteaux","year":"1988","unstructured":"Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8(8):2804\u20132815","journal-title":"J Neurosci"},{"issue":"3","key":"3495_CR2","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/s0304-3940(98)00504-7","volume":"251","author":"MG Spillantini","year":"1998","unstructured":"Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson\u2019s disease and dementia with Lewy bodies. Neurosci Lett 251(3):205\u2013208. https:\/\/doi.org\/10.1016\/s0304-3940(98)00504-7","journal-title":"Neurosci Lett"},{"issue":"11","key":"3495_CR3","doi-asserted-by":"publisher","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","volume":"95","author":"MG Spillantini","year":"1998","unstructured":"Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson\u2019s disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A 95(11):6469\u20136473. https:\/\/doi.org\/10.1073\/pnas.95.11.6469","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3495_CR4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.conb.2015.07.007","volume":"36","author":"U Dettmer","year":"2016","unstructured":"Dettmer U, Selkoe D, Bartels T (2016) New insights into cellular alpha-synuclein homeostasis in health and disease. Curr Opin Neurobiol 36:15\u201322. https:\/\/doi.org\/10.1016\/j.conb.2015.07.007","journal-title":"Curr Opin Neurobiol"},{"issue":"4","key":"3495_CR5","doi-asserted-by":"publisher","first-page":"699","DOI":"10.3233\/JPD-150642","volume":"5","author":"J Burre","year":"2015","unstructured":"Burre J (2015) The synaptic function of alpha-synuclein. J Parkinsons Dis 5(4):699\u2013713. https:\/\/doi.org\/10.3233\/JPD-150642","journal-title":"J Parkinsons Dis"},{"issue":"32","key":"3495_CR6","doi-asserted-by":"publisher","first-page":"10209","DOI":"10.1021\/bi020139h","volume":"41","author":"TT Ding","year":"2002","unstructured":"Ding TT, Lee SJ, Rochet JC, Lansbury PT Jr (2002) Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes. Biochemistry 41(32):10209\u201310217. https:\/\/doi.org\/10.1021\/bi020139h","journal-title":"Biochemistry"},{"issue":"5321","key":"3495_CR7","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","volume":"276","author":"MH Polymeropoulos","year":"1997","unstructured":"Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson\u2019s disease. Science 276(5321):2045\u20132047. https:\/\/doi.org\/10.1126\/science.276.5321.2045","journal-title":"Science"},{"issue":"5646","key":"3495_CR8","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1126\/science.1090278","volume":"302","author":"AB Singleton","year":"2003","unstructured":"Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T et al (2003) alpha-Synuclein locus triplication causes Parkinson\u2019s disease. Science 302(5646):841. https:\/\/doi.org\/10.1126\/science.1090278","journal-title":"Science"},{"issue":"10","key":"3495_CR9","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1021\/cn400066t","volume":"4","author":"E Hellstrand","year":"2013","unstructured":"Hellstrand E, Grey M, Ainalem ML, Ankner J, Forsyth VT, Fragneto G, Haertlein M, Dauvergne MT et al (2013) Adsorption of alpha-synuclein to supported lipid bilayers: positioning and role of electrostatics. ACS Chem Neurosci 4(10):1339\u20131351. https:\/\/doi.org\/10.1021\/cn400066t","journal-title":"ACS Chem Neurosci"},{"key":"3495_CR10","doi-asserted-by":"publisher","unstructured":"Grozdanov V, Bousset L, Hoffmeister M, Bliederhaeuser C, Meier C, Madiona K, Pieri L, Kiechle M et al (2019) Increased immune activation by pathologic alpha-Synuclein in Parkinson\u2019s disease. Ann Neurol. https:\/\/doi.org\/10.1002\/ana.25557","DOI":"10.1002\/ana.25557"},{"issue":"6645","key":"3495_CR11","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","volume":"388","author":"MG Spillantini","year":"1997","unstructured":"Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839\u2013840. https:\/\/doi.org\/10.1038\/42166","journal-title":"Nature"},{"issue":"1","key":"3495_CR12","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/s0304-3940(99)00208-6","volume":"265","author":"H Braak","year":"1999","unstructured":"Braak H, Sandmann-Keil D, Gai W, Braak E (1999) Extensive axonal Lewy neurites in Parkinson\u2019s disease: a novel pathological feature revealed by alpha-synuclein immunocytochemistry. Neurosci Lett 265(1):67\u201369. https:\/\/doi.org\/10.1016\/s0304-3940(99)00208-6","journal-title":"Neurosci Lett"},{"issue":"5651","key":"3495_CR13","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1126\/science.1090439","volume":"302","author":"TF Outeiro","year":"2003","unstructured":"Outeiro TF, Lindquist S (2003) Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302(5651):1772\u20131775. https:\/\/doi.org\/10.1126\/science.1090439","journal-title":"Science"},{"issue":"6161","key":"3495_CR14","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1126\/science.1245321","volume":"342","author":"DF Tardiff","year":"2013","unstructured":"Tardiff DF, Jui NT, Khurana V, Tambe MA, Thompson ML, Chung CY, Kamadurai HB, Kim HT et al (2013) Yeast reveal a \u201cdruggable\u201d Rsp5\/Nedd4 network that ameliorates alpha-synuclein toxicity in neurons. Science 342(6161):979\u2013983. https:\/\/doi.org\/10.1126\/science.1245321","journal-title":"Science"},{"issue":"2","key":"3495_CR15","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1073\/pnas.0711018105","volume":"105","author":"S Hamamichi","year":"2008","unstructured":"Hamamichi S, Rivas RN, Knight AL, Cao S, Caldwell KA, Caldwell GA (2008) Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson\u2019s disease model. Proc Natl Acad Sci U S A 105(2):728\u2013733. https:\/\/doi.org\/10.1073\/pnas.0711018105","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"19","key":"3495_CR16","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1093\/hmg\/ddn198","volume":"17","author":"T Kuwahara","year":"2008","unstructured":"Kuwahara T, Koyama A, Koyama S, Yoshina S, Ren CH, Kato T, Mitani S et al (2008) A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in alpha-synuclein transgenic C. elegans. Hum Mol Genet 17(19):2997\u20133009. https:\/\/doi.org\/10.1093\/hmg\/ddn198","journal-title":"Hum Mol Genet"},{"issue":"5556","key":"3495_CR17","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1126\/science.1067389","volume":"295","author":"PK Auluck","year":"2002","unstructured":"Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson\u2019s disease. Science 295(5556):865\u2013868. https:\/\/doi.org\/10.1126\/science.1067389","journal-title":"Science"},{"issue":"6","key":"3495_CR18","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1523\/JNEUROSCI.2606-11.2012","volume":"32","author":"AJ Harrington","year":"2012","unstructured":"Harrington AJ, Yacoubian TA, Slone SR, Caldwell KA, Caldwell GA (2012) Functional analysis of VPS41-mediated neuroprotection in Caenorhabditis elegans and mammalian models of Parkinson\u2019s disease. J Neurosci 32(6):2142\u20132153. https:\/\/doi.org\/10.1523\/JNEUROSCI.2606-11.2012","journal-title":"J Neurosci"},{"issue":"46","key":"3495_CR19","doi-asserted-by":"publisher","first-page":"27582","DOI":"10.1074\/jbc.M114.636027","volume":"290","author":"B Moree","year":"2015","unstructured":"Moree B, Yin G, Lazaro DF, Munari F, Strohaker T, Giller K, Becker S, Outeiro TF et al (2015) Small molecules detected by second-harmonic generation modulate the conformation of monomeric alpha-synuclein and reduce its aggregation in cells. J Biol Chem 290(46):27582\u201327593. https:\/\/doi.org\/10.1074\/jbc.M114.636027","journal-title":"J Biol Chem"},{"issue":"6","key":"3495_CR20","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s00401-013-1114-9","volume":"125","author":"J Wagner","year":"2013","unstructured":"Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, Prix C, Pan-Montojo F et al (2013) Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson\u2019s disease. Acta Neuropathol 125(6):795\u2013813. https:\/\/doi.org\/10.1007\/s00401-013-1114-9","journal-title":"Acta Neuropathol"},{"issue":"41","key":"3495_CR21","doi-asserted-by":"publisher","first-page":"10481","DOI":"10.1073\/pnas.1804198115","volume":"115","author":"J Pujols","year":"2018","unstructured":"Pujols J, Pena-Diaz S, Lazaro DF, Peccati F, Pinheiro F, Gonzalez D, Carija A, Navarro S et al (2018) Small molecule inhibits alpha-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons. Proc Natl Acad Sci U S A 115(41):10481\u201310486. https:\/\/doi.org\/10.1073\/pnas.1804198115","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"3495_CR22","doi-asserted-by":"publisher","first-page":"11469","DOI":"10.1038\/s41598-017-11664-5","volume":"7","author":"M Hollerhage","year":"2017","unstructured":"Hollerhage M, Moebius C, Melms J, Chiu WH, Goebel JN, Chakroun T, Koeglsperger T, Oertel WH et al (2017) Protective efficacy of phosphodiesterase-1 inhibition against alpha-synuclein toxicity revealed by compound screening in LUHMES cells. Sci Rep 7(1):11469. https:\/\/doi.org\/10.1038\/s41598-017-11664-5","journal-title":"Sci Rep"},{"key":"3495_CR23","doi-asserted-by":"publisher","unstructured":"Kerppola TK (2006) Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells. Nat Protoc 1(3):1278\u20131286. https:\/\/doi.org\/10.1038\/nprot.2006.201","DOI":"10.1038\/nprot.2006.201"},{"issue":"4","key":"3495_CR24","doi-asserted-by":"publisher","first-page":"e1867","DOI":"10.1371\/journal.pone.0001867","volume":"3","author":"TF Outeiro","year":"2008","unstructured":"Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ (2008) Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One 3(4):e1867. https:\/\/doi.org\/10.1371\/journal.pone.0001867","journal-title":"PLoS One"},{"issue":"5","key":"3495_CR25","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16(5):284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118","journal-title":"OMICS"},{"issue":"9","key":"3495_CR26","doi-asserted-by":"publisher","first-page":"6371","DOI":"10.1074\/jbc.M112.403311","volume":"288","author":"U Dettmer","year":"2013","unstructured":"Dettmer U, Newman AJ, Luth ES, Bartels T, Selkoe D (2013) In vivo cross-linking reveals principally oligomeric forms of alpha-synuclein and beta-synuclein in neurons and non-neural cells. J Biol Chem 288(9):6371\u20136385. https:\/\/doi.org\/10.1074\/jbc.M112.403311","journal-title":"J Biol Chem"},{"issue":"1","key":"3495_CR27","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.bbamcr.2016.11.003","volume":"1864","author":"L Seipold","year":"2017","unstructured":"Seipold L, Damme M, Prox J, Rabe B, Kasparek P, Sedlacek R, Altmeppen H, Willem M et al (2017) Tetraspanin 3: a central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein. Biochim Biophys Acta Mol Cell Res 1864(1):217\u2013230. https:\/\/doi.org\/10.1016\/j.bbamcr.2016.11.003","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"issue":"6","key":"3495_CR28","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/j.1600-0854.2010.01056.x","volume":"11","author":"P Kozik","year":"2010","unstructured":"Kozik P, Francis RW, Seaman MN, Robinson MS (2010) A screen for endocytic motifs. Traffic 11(6):843\u2013855. https:\/\/doi.org\/10.1111\/j.1600-0854.2010.01056.x","journal-title":"Traffic"},{"issue":"27","key":"3495_CR29","doi-asserted-by":"publisher","first-page":"25009","DOI":"10.1074\/jbc.M300227200","volume":"278","author":"JL Webb","year":"2003","unstructured":"Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC (2003) Alpha-Synuclein is degraded by both autophagy and the proteasome. J Biol Chem 278(27):25009\u201325013. https:\/\/doi.org\/10.1074\/jbc.M300227200","journal-title":"J Biol Chem"},{"issue":"6369","key":"3495_CR30","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1126\/science.aan6160","volume":"358","author":"G Fusco","year":"2017","unstructured":"Fusco G, Chen SW, Williamson PTF, Cascella R, Perni M, Jarvis JA, Cecchi C, Vendruscolo M et al (2017) Structural basis of membrane disruption and cellular toxicity by alpha-synuclein oligomers. Science 358(6369):1440\u20131443. https:\/\/doi.org\/10.1126\/science.aan6160","journal-title":"Science"},{"issue":"19","key":"3495_CR31","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.1242\/jcs.167981","volume":"128","author":"NK Thiede-Stan","year":"2015","unstructured":"Thiede-Stan NK, Tews B, Albrecht D, Ristic Z, Ewers H, Schwab ME (2015) Tetraspanin-3 is an organizer of the multi-subunit Nogo-A signaling complex. J Cell Sci 128(19):3583\u20133596. https:\/\/doi.org\/10.1242\/jcs.167981","journal-title":"J Cell Sci"},{"issue":"1","key":"3495_CR32","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s40478-018-0578-1","volume":"6","author":"C Masaracchia","year":"2018","unstructured":"Masaracchia C, Hnida M, Gerhardt E, Lopes da Fonseca T, Villar-Pique A, Branco T, Stahlberg MA, Dean C et al (2018) Membrane binding, internalization, and sorting of alpha-synuclein in the cell. Acta Neuropathol Commun 6(1):79. https:\/\/doi.org\/10.1186\/s40478-018-0578-1","journal-title":"Acta Neuropathol Commun"},{"key":"3495_CR33","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1146\/annurev-biochem-062917-012644","volume":"87","author":"M Mettlen","year":"2018","unstructured":"Mettlen M, Chen PH, Srinivasan S, Danuser G, Schmid SL (2018) Regulation of clathrin-mediated endocytosis. Annu Rev Biochem 87:871\u2013896. https:\/\/doi.org\/10.1146\/annurev-biochem-062917-012644","journal-title":"Annu Rev Biochem"},{"issue":"20","key":"3495_CR34","doi-asserted-by":"publisher","first-page":"6838","DOI":"10.1523\/JNEUROSCI.5699-09.2010","volume":"30","author":"E Emmanouilidou","year":"2010","unstructured":"Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, Stefanis L, Vekrellis K (2010) Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 30(20):6838\u20136851. https:\/\/doi.org\/10.1523\/JNEUROSCI.5699-09.2010","journal-title":"J Neurosci"},{"issue":"17","key":"3495_CR35","doi-asserted-by":"publisher","first-page":"3481","DOI":"10.1038\/emboj.2011.286","volume":"30","author":"J Huotari","year":"2011","unstructured":"Huotari J, Helenius A (2011) Endosome maturation. EMBO J 30(17):3481\u20133500. https:\/\/doi.org\/10.1038\/emboj.2011.286","journal-title":"EMBO J"},{"issue":"29","key":"3495_CR36","doi-asserted-by":"publisher","first-page":"27441","DOI":"10.1074\/jbc.M101318200","volume":"276","author":"JY Sung","year":"2001","unstructured":"Sung JY, Kim J, Paik SR, Park JH, Ahn YS, Chung KC (2001) Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. J Biol Chem 276(29):27441\u201327448. https:\/\/doi.org\/10.1074\/jbc.M101318200","journal-title":"J Biol Chem"},{"issue":"6","key":"3495_CR37","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s00109-013-1038-9","volume":"91","author":"SE Eisbach","year":"2013","unstructured":"Eisbach SE, Outeiro TF (2013) Alpha-synuclein and intracellular trafficking: impact on the spreading of Parkinson\u2019s disease pathology. J Mol Med (Berl) 91(6):693\u2013703. https:\/\/doi.org\/10.1007\/s00109-013-1038-9","journal-title":"J Mol Med (Berl)"},{"issue":"4","key":"3495_CR38","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1093\/jnen\/63.4.302","volume":"63","author":"E Dalfo","year":"2004","unstructured":"Dalfo E, Gomez-Isla T, Rosa JL, Nieto Bodelon M, Cuadrado Tejedor M, Barrachina M, Ambrosio S, Ferrer I (2004) Abnormal alpha-synuclein interactions with Rab proteins in alpha-synuclein A30P transgenic mice. J Neuropathol Exp Neurol 63(4):302\u2013313. https:\/\/doi.org\/10.1093\/jnen\/63.4.302","journal-title":"J Neuropathol Exp Neurol"},{"key":"3495_CR39","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3389\/fncel.2017.00081","volume":"11","author":"MM Shi","year":"2017","unstructured":"Shi MM, Shi CH, Xu YM (2017) Rab GTPases: the key players in the molecular pathway of Parkinson\u2019s disease. Front Cell Neurosci 11:81. https:\/\/doi.org\/10.3389\/fncel.2017.00081","journal-title":"Front Cell Neurosci"},{"issue":"23","key":"3495_CR40","doi-asserted-by":"publisher","first-page":"5544","DOI":"10.1523\/JNEUROSCI.0482-05.2005","volume":"25","author":"WW Smith","year":"2005","unstructured":"Smith WW, Margolis RL, Li X, Troncoso JC, Lee MK, Dawson VL, Dawson TM, Iwatsubo T et al (2005) Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells. J Neurosci 25(23):5544\u20135552. https:\/\/doi.org\/10.1523\/JNEUROSCI.0482-05.2005","journal-title":"J Neurosci"},{"issue":"10","key":"3495_CR41","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1172\/JCI15777","volume":"110","author":"M Neumann","year":"2002","unstructured":"Neumann M, Kahle PJ, Giasson BI, Ozmen L, Borroni E, Spooren W, Muller V, Odoy S et al (2002) Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J Clin Invest 110(10):1429\u20131439. https:\/\/doi.org\/10.1172\/JCI15777","journal-title":"J Clin Invest"},{"issue":"8","key":"3495_CR42","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1523\/JNEUROSCI.3809-03.2004","volume":"24","author":"HJ Lee","year":"2004","unstructured":"Lee HJ, Khoshaghideh F, Patel S, Lee SJ (2004) Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway. J Neurosci 24(8):1888\u20131896. https:\/\/doi.org\/10.1523\/JNEUROSCI.3809-03.2004","journal-title":"J Neurosci"},{"issue":"20","key":"3495_CR43","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.1038\/emboj.2009.257","volume":"28","author":"DP Karpinar","year":"2009","unstructured":"Karpinar DP, Balija MB, Kugler S, Opazo F, Rezaei-Ghaleh N, Wender N, Kim HY, Taschenberger G et al (2009) Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson\u2019s disease models. EMBO J 28(20):3256\u20133268. https:\/\/doi.org\/10.1038\/emboj.2009.257","journal-title":"EMBO J"},{"issue":"10","key":"3495_CR44","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1073\/pnas.1100976108","volume":"108","author":"B Winner","year":"2011","unstructured":"Winner B, Jappelli R, Maji SK, Desplats PA, Boyer L, Aigner S, Hetzer C, Loher T et al (2011) In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A 108(10):4194\u20134199. https:\/\/doi.org\/10.1073\/pnas.1100976108","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"3495_CR45","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/s0022-2836(02)00735-0","volume":"322","author":"HA Lashuel","year":"2002","unstructured":"Lashuel HA, Petre BM, Wall J, Simon M, Nowak RJ, Walz T, Lansbury PT Jr (2002) Alpha-synuclein, especially the Parkinson\u2019s disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol 322(5):1089\u20131102. https:\/\/doi.org\/10.1016\/s0022-2836(02)00735-0","journal-title":"J Mol Biol"},{"issue":"5785","key":"3495_CR46","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1126\/science.1129462","volume":"313","author":"AA Cooper","year":"2006","unstructured":"Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K et al (2006) Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson\u2019s models. Science 313(5785):324\u2013328. https:\/\/doi.org\/10.1126\/science.1129462","journal-title":"Science"},{"issue":"1","key":"3495_CR47","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s00401-017-1704-z","volume":"134","author":"S Paillusson","year":"2017","unstructured":"Paillusson S, Gomez-Suaga P, Stoica R, Little D, Gissen P, Devine MJ, Noble W, Hanger DP et al (2017) alpha-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca(2+) homeostasis and mitochondrial ATP production. Acta Neuropathol 134(1):129\u2013149. https:\/\/doi.org\/10.1007\/s00401-017-1704-z","journal-title":"Acta Neuropathol"},{"issue":"2","key":"3495_CR48","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1159\/000325028","volume":"19","author":"JY Chung","year":"2011","unstructured":"Chung JY, Lee SJ, Lee SH, Jung YS, Ha NC, Seol W, Park BJ (2011) Direct interaction of alpha-synuclein and AKT regulates IGF-1 signaling: implication of Parkinson disease. Neurosignals 19(2):86\u201396. https:\/\/doi.org\/10.1159\/000325028","journal-title":"Neurosignals"},{"issue":"4","key":"3495_CR49","doi-asserted-by":"publisher","first-page":"363","DOI":"10.18632\/aging.100045","volume":"1","author":"A Currais","year":"2009","unstructured":"Currais A, Hortobagyi T, Soriano S (2009) The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer\u2019s disease. Aging (Albany NY) 1(4):363\u2013371. https:\/\/doi.org\/10.18632\/aging.100045","journal-title":"Aging (Albany NY)"},{"issue":"3","key":"3495_CR50","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.bbrc.2009.05.089","volume":"385","author":"SY Kao","year":"2009","unstructured":"Kao SY (2009) Rescue of alpha-synuclein cytotoxicity by insulin-like growth factors. Biochem Biophys Res Commun 385(3):434\u2013438. https:\/\/doi.org\/10.1016\/j.bbrc.2009.05.089","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"3495_CR51","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1002\/jnr.20141","volume":"77","author":"SK Tiwari-Woodruff","year":"2004","unstructured":"Tiwari-Woodruff SK, Kaplan R, Kornblum HI, Bronstein JM (2004) Developmental expression of OAP-1\/Tspan-3, a member of the tetraspanin superfamily. J Neurosci Res 77(2):166\u2013173. https:\/\/doi.org\/10.1002\/jnr.20141","journal-title":"J Neurosci Res"},{"issue":"9","key":"3495_CR52","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1016\/j.yexcr.2008.09.020","volume":"315","author":"MS Pols","year":"2009","unstructured":"Pols MS, Klumperman J (2009) Trafficking and function of the tetraspanin CD63. Exp Cell Res 315(9):1584\u20131592. https:\/\/doi.org\/10.1016\/j.yexcr.2008.09.020","journal-title":"Exp Cell Res"},{"issue":"Pt 17","key":"3495_CR53","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1242\/jcs.154906","volume":"127","author":"S Charrin","year":"2014","unstructured":"Charrin S, Jouannet S, Boucheix C, Rubinstein E (2014) Tetraspanins at a glance. J Cell Sci 127(Pt 17):3641\u20133648. https:\/\/doi.org\/10.1242\/jcs.154906","journal-title":"J Cell Sci"},{"issue":"5","key":"3495_CR54","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/s0896-6273(00)80472-9","volume":"20","author":"Y Fujita","year":"1998","unstructured":"Fujita Y, Shirataki H, Sakisaka T, Asakura T, Ohya T, Kotani H, Yokoyama S, Nishioka H et al (1998) Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process. Neuron 20(5):905\u2013915. https:\/\/doi.org\/10.1016\/s0896-6273(00)80472-9","journal-title":"Neuron"},{"issue":"6","key":"3495_CR55","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/nrm1929","volume":"7","author":"TK Kerppola","year":"2006","unstructured":"Kerppola TK (2006) Visualization of molecular interactions by fluorescence complementation. Nat Rev Mol Cell Biol 7(6):449\u2013456. https:\/\/doi.org\/10.1038\/nrm1929","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"8","key":"3495_CR56","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","unstructured":"Sanjana NE, Shalem O, Zhang F (2014) Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods 11(8):783\u2013784. https:\/\/doi.org\/10.1038\/nmeth.3047","journal-title":"Nat Methods"},{"key":"3495_CR57","doi-asserted-by":"publisher","unstructured":"Chen M, Amado N, Tan J, Reis A, Ge M, Abreu JG, He X (2020) TMEM79\/MATTRIN defines a pathway for Frizzled regulation and is required for Xenopus embryogenesis. Elife 9. https:\/\/doi.org\/10.7554\/eLife.56793","DOI":"10.7554\/eLife.56793"},{"key":"3495_CR58","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fphar.2019.00016","volume":"10","author":"NN Yuan","year":"2019","unstructured":"Yuan NN, Cai CZ, Wu MY, Zhu Q, Su H, Li M, Ren J et al (2019) Canthin-6-one accelerates alpha-synuclein degradation by enhancing UPS activity: drug target identification by CRISPR-Cas9 whole genome-wide screening technology. Front Pharmacol 10:16. https:\/\/doi.org\/10.3389\/fphar.2019.00016","journal-title":"Front Pharmacol"},{"issue":"6","key":"3495_CR59","doi-asserted-by":"publisher","first-page":"9184","DOI":"10.1002\/jcp.27595","volume":"234","author":"M Cai","year":"2019","unstructured":"Cai M, Li S, Shuai Y, Li J, Tan J, Zeng Q (2019) Genome-wide CRISPR-Cas9 viability screen reveals genes involved in TNF-alpha-induced apoptosis of human umbilical vein endothelial cells. J Cell Physiol 234(6):9184\u20139193. https:\/\/doi.org\/10.1002\/jcp.27595","journal-title":"J Cell Physiol"},{"issue":"6166","key":"3495_CR60","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1247005","volume":"343","author":"O Shalem","year":"2014","unstructured":"Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelson T, Heckl D, Ebert BL et al (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343(6166):84\u201387. https:\/\/doi.org\/10.1126\/science.1247005","journal-title":"Science"},{"issue":"12","key":"3495_CR61","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1186\/s13059-014-0554-4","volume":"15","author":"W Li","year":"2014","unstructured":"Li W, Xu H, Xiao T, Cong L, Love MI, Zhang F, Irizarry RA, Liu JS et al (2014) MAGeCK enables robust identification of essential genes from genome-scale CRISPR\/Cas9 knockout screens. Genome Biol 15(12):554. https:\/\/doi.org\/10.1186\/s13059-014-0554-4","journal-title":"Genome Biol"},{"issue":"4","key":"3495_CR62","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1073\/pnas.1700465115","volume":"115","author":"S Kim","year":"2018","unstructured":"Kim S, Yun SP, Lee S, Umanah GE, Bandaru VVR, Yin X, Rhee P, Karuppagounder SS et al (2018) GBA1 deficiency negatively affects physiological alpha-synuclein tetramers and related multimers. Proc Natl Acad Sci U S A 115(4):798\u2013803. https:\/\/doi.org\/10.1073\/pnas.1700465115","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3495_CR63","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-1-4939-9124-2_8","volume":"1948","author":"T Imberdis","year":"2019","unstructured":"Imberdis T, Fanning S, Newman A, Ramalingam N, Dettmer U (2019) Studying alpha-Synuclein conformation by intact-cell cross-linking. Methods Mol Biol 1948:77\u201391. https:\/\/doi.org\/10.1007\/978-1-4939-9124-2_8","journal-title":"Methods Mol Biol"},{"issue":"41","key":"3495_CR64","doi-asserted-by":"publisher","first-page":"21616","DOI":"10.1074\/jbc.M116.733410","volume":"291","author":"T Zhang","year":"2016","unstructured":"Zhang T, Xue L, Li L, Tang C, Wan Z, Wang R, Tan J, Tan Y et al (2016) BNIP3 protein suppresses PINK1 kinase proteolytic cleavage to promote mitophagy. J Biol Chem 291(41):21616\u201321629. https:\/\/doi.org\/10.1074\/jbc.M116.733410","journal-title":"J Biol Chem"},{"key":"3495_CR65","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.neulet.2017.06.034","volume":"655","author":"J Zhang","year":"2017","unstructured":"Zhang J, Lei H, Chen Y, Ma YT, Jiang F, Tan J, Zhang Y, Li JD (2017) Enzymatic O-GlcNAcylation of alpha-synuclein reduces aggregation and increases SDS-resistant soluble oligomers. Neurosci Lett 655:90\u201394. https:\/\/doi.org\/10.1016\/j.neulet.2017.06.034","journal-title":"Neurosci Lett"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03495-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-023-03495-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03495-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T05:32:31Z","timestamp":1695792751000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-023-03495-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":65,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["3495"],"URL":"https:\/\/doi.org\/10.1007\/s12035-023-03495-5","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]},"assertion":[{"value":"25 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}