Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation
Open accessAbstract
β-Sheet-rich α-synuclein (αS) aggregates characterize Parkinson’s disease (PD). αS was long believed to be a natively unfolded monomer, but recent work suggests it also occurs in α-helix-rich tetramers. Crosslinking traps principally tetrameric αS in intact normal neurons, but not after cell lysis, suggesting a dynamic equilibrium. Here we show that freshly biopsied normal human brain contains abundant αS tetramers. The PD-causing mutation A53T decreases tetramers in mouse brain. Neurons derived from an A53T patient have decreased tetramers. Neurons expressing E46K do also, and adding 1-2 E46K-like mutations into the canonical αS repeat motifs (KTKEGV) further reduces tetramers, decreases αS solubility and induces neurotoxicity and round inclusions. The other three fPD missense mutations likewise decrease tetramer:monomer ratios. The destabilization of physiological tetramers by PD-causing missense mutations and the neurotoxicity and inclusions induced by markedly decreasing tetramers suggest that decreased α-helical tetramers and increased unfolded monomers initiate pathogenesis. Tetramer-stabilizing compounds should prevent this.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In human brain lysates, human neuronal cultures, mouse models, and cell lines expressing familial PD αSyn mutations (A53T or E46K), a decrease in the tetramer:monomer ratio correlates with increased neurotoxicity.
“in human brain lysates, human neuronal cultures, mouse models, and in mouse/human/goat cell lines expressing familial PD αSyn mutations (A53T or E46K), a decrease in the tetramer:monomer ratio correlated to increased neurotoxicity”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [139]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638 · see citing works
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382 · see citing works
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240 · see citing works
α-Synuclein Locus Triplication Causes Parkinson's Disease
Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., et al. (2003) · Science · doi:10.1126/science.1090278 · Cited by 4,383 · see citing works
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836 · see citing works
The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia
Zarranz, J. J., Alegre, J., Gómez‐Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atarés, B., et al. (2004) · Annals of Neurology · doi:10.1002/ana.10795 · Cited by 2,737 · see citing works
Stabilization of α-Synuclein Secondary Structure upon Binding to Synthetic Membranes
Davidson, W. S., Jonas, A., Clayton, D. F., & George, J. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.16.9443 · Cited by 1,588 · see citing works
NACP, A Protein Implicated in Alzheimer's Disease and Learning, Is Natively Unfolded
Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A., & Lansbury, P. T. (1996) · Biochemistry · doi:10.1021/bi961799n · Cited by 1,524 · see citing works
α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation
Bartels, T., Choi, J. G., & Selkoe, D. J. (2011) · Nature · doi:10.1038/nature10324 · Cited by 1,263 · see citing works
Self-citationHockemeyer, D. F., Soldner, F., Beard, C., Gao, Q., Mitalipova, M. M., DeKelver, R. C., Katibah, G. E., Amora, R., Boydston, E. A., Zeitler, B., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1562 · Cited by 1,035 · see citing works
Self-citationGeorge, J. M., Jin, H., Woods, W. S., & Clayton, D. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90040-3 · Cited by 844 · see citing works
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825 · see citing works
Conway, K. A., Harper, J. D., & Lansbury, P. T. (2000) · Biochemistry · doi:10.1021/bi991447r · Cited by 786 · see citing works
Soldner, F., Laganière, J., Cheng, A. W., Hockemeyer, D., Gao, Q., Alagappan, R., Khurana, V., Golbe, L. I., Myers, R. H., Lindquist, S., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.019 · Cited by 728 · see citing works
Self-citationAlpha‐synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease
Appel‐Cresswell, S., Vilariño‐Güell, C., Encarnacion, M. J., Sherman, H. E., Yu, I. S., Shah, B., Weir, D. M., Thompson, C., Szu‐Tu, C., Trinh, J., et al. (2013) · Movement Disorders · doi:10.1002/mds.25421 · Cited by 669 · see citing works
Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Schindzielorz, A., Okochi, M., Leimer, U., van der Putten, H., Probst, A., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06365.2000 · Cited by 641 · see citing works
Fauvet, B., Mbefo, M. K., Fares, M.-B., Desobry, C., Michael, S. A., Ardah, M. T., Tsika, E., Coune, P., Prudent, M., Lion, N., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.318949 · Cited by 565 · see citing works
A soluble α-synuclein construct forms a dynamic tetramer
Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L. T. T., Liao, J., Auclair, J. R., Johnson, D., Landeru, A., Simorellis, A. K., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113260108 · Cited by 478 · see citing works
Burré, J., Sharma, M., & Südhof, T. C. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416598111 · Cited by 478 · see citing works
A novel α-synuclein missense mutation in Parkinson disease
Proukakis, C., Dudzik, C. G., Brier, T., Mackay, D. S., Cooper, J. A. D., Millhauser, G. L., Houlden, H., & Schapira, A. H. V. (2013) · Neurology · doi:10.1212/wnl.0b013e31828727ba · Cited by 465 · see citing works
Kiely, A. P., Asi, Y. T., Kara, E., Limousin, P. D., Ling, H., Lewis, P. A., Proukakis, C., Quinn, N. P., Lees, A. J., Hardy, J., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1096-7 · Cited by 450 · see citing works
Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation
Borhani, D. W., Rogers, D. P., Engler, J. A., & Brouillette, C. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12291 · Cited by 434 · see citing works
Visualization of molecular interactions by fluorescence complementation
Kerppola, T. K. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1929 · Cited by 430 · see citing works
Formation of Toxic Oligomeric α-Synuclein Species in Living Cells
Outeiro, T. F., Putcha, P., Tetzlaff, J. E., Spoelgen, R., Koker, M., Carvalho, F. L. F., Hyman, B. T., & McLean, P. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001867 · Cited by 400 · see citing works
Properties of native brain α-synuclein
Burré, J., Vivona, S., Diao, J., Sharma, M., Brünger, A. T., & Südhof, T. C. (2013) · Nature · doi:10.1038/nature12125 · Cited by 340 · see citing works
Johnson, S. M., Connelly, S., Fearns, C., Powers, E. T., & Kelly, J. W. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.12.060 · Cited by 326 · see citing works
DeKelver, R. C., Choi, V. M., Moehle, E. A., Paschon, D. E., Hockemeyer, D. F., Meijsing, S. H., Sancak, Y., Cui, X., Steine, E. J., Miller, J. C., et al. (2010) · Genome Research · doi:10.1101/gr.106773.110 · Cited by 310 · see citing works
Self-citationKuo, Y., Li, Z., Jiao, Y., Gaborit, N., Pani, A. K., Orrison, B. M., Bruneau, B. G., Giasson, B. I., Smeyne, R. J., Gershon, M. D., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq038 · Cited by 288 · see citing works
α-Synuclein Multimers Cluster Synaptic Vesicles and Attenuate Recycling
Wang, L., Das, U., Scott, D. A., Tang, Y., McLean, P. J., & Roy, S. (2014) · Current Biology · doi:10.1016/j.cub.2014.08.027 · Cited by 275 · see citing works
The p53 protein is an unusually shaped tetramer that binds directly to DNA.
Friedman, P. N., Chen, X., Bargonetti, J., & Prives, C. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3319 · Cited by 264 · see citing works
Genetic variability in the SNCA gene influences α‐synuclein levels in the blood and brain
Fuchs, J., Tichopád, A., Golub, Y., Munz, M., Schweitzer, K. J., Wolf, B., Berg, D., Mueller, J. C., & Gasser, T. (2007) · The FASEB Journal · doi:10.1096/fj.07-9348com · Cited by 247 · see citing works
Dettmer, U., Newman, A. J., Luth, E. S., Bartels, T., & Selkoe, D. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.403311 · Cited by 221 · see citing works
Self-citationIrizarry, M. C., Kim, T., McNamara, M. J., Tanzi, R. E., George, J. M., Clayton, D. F., & Hyman, B. T. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199608000-00004 · Cited by 205 · see citing works
Monomeric Synucleins Generate Membrane Curvature
Westphal, C. H., & Chandra, S. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.418871 · Cited by 199 · see citing works
Chang, C., Manlandro, C. M., Arnoult, D., Stadler, J., Posey, A. E., Hill, R. B., & Blackstone, C. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.142430 · Cited by 180 · see citing works
Improved Immunodetection of Endogenous α-Synuclein
Lee, B. R., & Kamitani, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023939 · Cited by 155 · see citing works
The role of apolipoprotein AI domains in lipid binding
Davidson, W. S., Hazlett, T. L., Mantulin, W. W., & Jonas, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13605 · Cited by 139 · see citing works
Activation and control of p53 tetramerization in individual living cells
Gaglia, G., Guan, Y., Shah, J. V., & Lahav, G. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311126110 · Cited by 126 · see citing works
The Dynamic Structure of α-Synuclein Multimers
Gurry, T., Ullman, O., Fisher, C. K., Perovic, I., Pochapsky, T. C., & Stultz, C. M. (2013) · Journal of the American Chemical Society · doi:10.1021/ja310518p · Cited by 107 · see citing works
Reprogramming of Postnatal Neurons into Induced Pluripotent Stem Cells by Defined Factors
Kim, J., Lengner, C. J., Kirak, O., Hanna, J. H., Cassady, J. P., Lodato, M. A., Wu, S., Faddah, D. A., Steine, E. J., Gao, Q., et al. (2011) · Stem Cells · doi:10.1002/stem.641 · Cited by 79 · see citing works
Self-citationCancer-associated p53 Tetramerization Domain Mutants
Kamada, R., Nomura, T., Anderson, C. W., & Sakaguchi, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.174698 · Cited by 79 · see citing works
Luth, E. S., Bartels, T., Dettmer, U., Kim, N. C., & Selkoe, D. J. (2014) · Biochemistry · doi:10.1021/bi501188a · Cited by 74 · see citing works
Self-citationDirect detection of alpha synuclein oligomers in vivo
Dimant, H., Kalia, S. K., Kalia, L. V., Zhu, L., Kibuuka, L. N., Ebrahimi‐Fakhari, D., McFarland, N. R., Fan, Z., Hyman, B. T., & McLean, P. J. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-6 · Cited by 74 · see citing works
Baulac, S., LaVoie, M. J., Strahle, J. M., Schlossmacher, M. G., & Xia, W. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.06.014 · Cited by 63 · see citing works
Transmembrane Protein 147 (TMEM147) Is a Novel Component of the Nicalin-NOMO Protein Complex
Dettmer, U., Kuhn, P., Abou‐Ajram, C., Lichtenthaler, S. F., Krüger, M., Kremmer, E., Haass, C., & Haffner, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.132548 · Cited by 57 · see citing works
Self-citationManning, L. R., Russell, J., Padovan, J. C., Chait, B. T., Popowicz, A. M., Manning, R. S., & Manning, J. M. (2007) · Protein Science · doi:10.1110/ps.072891007 · Cited by 51 · see citing works
α-Synuclein mutations cluster around a putative protein loop
Kara, E., Lewis, P. A., Ling, H., Proukakis, C., Houlden, H., & Hardy, J. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.04.058 · Cited by 45 · see citing works
Barbeau, D. L., Jonas, A., Teng, T.-L., & Scanu, A. M. (1979) · Biochemistry · doi:10.1021/bi00569a021 · Cited by 45 · see citing works
Kamada, R., Yoshino, W., Nomura, T., Chuman, Y., Imagawa, T., Suzuki, T., & Sakaguchi, K. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.06.053 · Cited by 43 · see citing works
A New Method for Quantitative Immunoblotting of Endogenous α-Synuclein
Newman, A. J., Selkoe, D. J., & Dettmer, U. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081314 · Cited by 39 · see citing works
Self-citationImpact of Self-association on Function of Apolipoprotein A-I
Jayaraman, S., Abe-Dohmae, S., Yokoyama, S., & Cavigiolio, G. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.262485 · Cited by 37 · see citing works
Specific Recognition of p53 Tetramers by Peptides Derived from p53 Interacting Proteins
Gabizon, R., Brandt, T., Sukenik, S., Lahav, N., Lebendiker, M., Shalev, D. E., Veprintsev, D. B., & Friedler, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038060 · Cited by 29 · see citing works
Bimolecular Fluorescence Complementation (BiFC) Analysis of Protein–Protein Interaction
Kodama, Y., & Hu, C. (2013) · Methods in cell biology · doi:10.1016/b978-0-12-407239-8.00006-9 · Cited by 17 · see citing works
The Tetramer of p53 in the Absence of DNA Forms a Relaxed Quaternary State
Pham, N., Moreno, A. L., Cheung, N., & Viadiu, H. (2012) · Biochemistry · doi:10.1021/bi301193k · Cited by 16 · see citing works
Muscolini, M., Montagni, E., Caristi, S., Nomura, T., Kamada, R., Agostino, S. D., Corazzari, M., Piacentini, M., Blandino, G., Costanzo, A., et al. (2009) · Cell Cycle · doi:10.4161/cc.8.20.9910 · Cited by 16 · see citing works
Defining the Oligomerization State of γ-Synuclein in Solution and in Cells
Golebiewska, U. P., Zurawsky, C., & Scarlata, S. (2013) · Biochemistry · doi:10.1021/bi401479a · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525 · see citing works
Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes
Shahmoradian, S. H., Lewis, A. J., Genoud, C., Hench, J., Moors, T. E., Navarro, P. P., Castaño‐Díez, D., Schweighauser, G., Graff-Meyer, A., Goldie, K. N., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0423-2 · Cited by 974 · see citing works
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897 · see citing works
Structural disorder of monomeric α-synuclein persists in mammalian cells
Theillet, F., Binolfi, A., Bekei, B., Martorana, A., Rose, H. M., Stuiver, M., Verzini, S., Lorenz, D., van Rossum, M., Goldfarb, D., et al. (2016) · Nature · doi:10.1038/nature16531 · Cited by 877 · see citing works
Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease
Rocha, E. M., Miranda, B. D., & Sanders, L. H. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.04.004 · Cited by 769 · see citing works
α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson’s disease
Di Maio, R., Barrett, P. J., Hoffman, E. K., Barrett, C. W., Zharikov, A., Borah, A., Hu, X., McCoy, J., Chu, C. T., Burton, E. A., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf3634 · Cited by 619 · see citing works
Defects in trafficking bridge Parkinson’s disease pathology and genetics
Abeliovich, A., & Gitler, A. D. (2016) · Nature · doi:10.1038/nature20414 · Cited by 462 · see citing works
β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease
Mittal, S., Bjørnevik, K., Im, D. S., Flierl, A., Dong, X., Locascio, J. J., Abo, K. M., Long, E., Jin, M., Xu, B. Y., et al. (2017) · Science · doi:10.1126/science.aaf3934 · Cited by 417 · see citing works
Self-citationReview: Sporadic Parkinson's disease: development and distribution ofα‐synuclein pathology
Tredici, K. D., & Braak, H. (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12298 · Cited by 396 · see citing works
α-synuclein in the pathophysiology of Alzheimer’s disease
Twohig, D., & Nielsen, H. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0320-x · Cited by 374 · see citing works
Neuropathology and molecular diagnosis of Synucleinopathies
Koga, S., Sekiya, H., Kondru, N. C., Ross, O. A., & Dickson, D. W. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00501-z · Cited by 345 · see citing works
The physiological role of α‐synuclein and its relationship to Parkinson’s Disease
Sulzer, D., & Edwards, R. H. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14810 · Cited by 310 · see citing works
Karagöz, G. E., Acosta‐Alvear, D., & Walter, P. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033886 · Cited by 302 · see citing works
Park, S. J. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s254808 · Cited by 296 · see citing works
A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration
Walsh, D. M., & Selkoe, D. J. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.13 · Cited by 290 · see citing works
Self-citationFanning, S., Haque, A., Imberdis, T., Baru, V., Barrasa, M. I., Nuber, S., Termine, D., Ramalingam, N., Ho, G. P. H., Noble, T., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.028 · Cited by 285 · see citing works
Self-citationAging and Parkinson's disease: Different sides of the same coin?
Collier, T. J., Kanaan, N. M., & Kordower, J. H. (2017) · Movement Disorders · doi:10.1002/mds.27037 · Cited by 271 · see citing works
Initiation and propagation of α-synuclein aggregation in the nervous system
Hijaz, B. A., & Volpicelli‐Daley, L. A. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00368-6 · Cited by 267 · see citing works
Parkinson’s disease: proteinopathy or lipidopathy?
Fanning, S., Selkoe, D. J., & Dettmer, U. (2020) · npj Parkinson s Disease · doi:10.1038/s41531-019-0103-7 · Cited by 238 · see citing works
Self-citationReversible Conformational Conversion of α-Synuclein into Toxic Assemblies by Glucosylceramide
Zunke, F., Moise, A. C., Belur, N. R., Gelyana, E., Stojkovska, I., Dzaferbegovic, H., Toker, N., Jeon, S., Fredriksen, K., & Mazzulli, J. R. (2017) · Neuron · doi:10.1016/j.neuron.2017.12.012 · Cited by 222 · see citing works
Reverse engineering Lewy bodies: how far have we come and how far can we go?
Fares, M. B., Jagannath, S., & Lashuel, H. A. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-00416-6 · Cited by 199 · see citing works
Cardiolipin exposure on the outer mitochondrial membrane modulates α-synuclein
Ryan, T. L., Bamm, V. V., Stykel, M. G., Coackley, C. L., Humphries, K. M., Jamieson-Williams, R., Ambasudhan, R., Mosser, D. D., Lipton, S. A., Harauz, G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03241-9 · Cited by 204 · see citing works
G2019S-LRRK2 Expression Augments -Synuclein Sequestration into Inclusions in Neurons
Volpicelli‐Daley, L. A., Abdelmotilib, H., Liu, Z., Stoyka, L. E., Daher, J. P. L., Milnerwood, A. J., Unni, V. K., Hirst, W. D., Yue, Z., Zhao, H., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3642-15.2016 · Cited by 185 · see citing works
The Parkinson Disease gene SNCA: Evolutionary and structural insights with pathological implication
Siddiqui, I. J., Pervaiz, N., & Abbasi, A. A. (2016) · Scientific Reports · doi:10.1038/srep24475 · Cited by 186 · see citing works
GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers
Kim, S., Yun, S. P., Lee, S., Umanah, G. K. E., Bandaru, V. V. R., Yin, X., Rhee, P., Karuppagounder, S. S., Kwon, S., Lee, H., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700465115 · Cited by 179 · see citing works
Genetic predispositions of Parkinson’s disease revealed in patient-derived brain cells
Tran, J., Anastacio, H. T. D., & Bardy, C. (2020) · npj Parkinson s Disease · doi:10.1038/s41531-020-0110-8 · Cited by 181 · see citing works
Synaptic failure and α‐synuclein
Calò, L., Węgrzynowicz, M., Santivañez‐Perez, J., & Spillantini, M. G. (2016) · Movement Disorders · doi:10.1002/mds.26479 · Cited by 170 · see citing works
Alpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease
Oliveira, L. M. A., Gasser, T., Edwards, R. H., Zweckstetter, M., Melki, R., Stefanis, L., Lashuel, H. A., Sulzer, D. L., Vekrellis, K., Halliday, G. M., et al. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00203-9 · Cited by 169 · see citing works
Extracellular Interactions of Alpha-Synuclein in Multiple System Atrophy
Valdinocci, D., Radford, R. A. W., Goulding, M., Hayashi, J., Chung, R. S., & Pountney, D. L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19124129 · Cited by 161 · see citing works
Kouroupi, G., Taoufik, E., Vlachos, I. S., Tsioras, K., Antoniou, N., Papastefanaki, F., Chroni-Tzartou, D., Wrasidlo, W., Bohl, D., Stellas, D., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617259114 · Cited by 145 · see citing works
Nuber, S., Rajsombath, M. M., Minakaki, G., Winkler, J., Müller, C. P., Ericsson, M., Caldarone, B. J., Dettmer, U., & Selkoe, D. J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.014 · Cited by 145 · see citing works
Self-citationCell-to-Cell Transmission of Tau and α-Synuclein
Uemura, N., Uemura, M. T., Luk, K. C., Lee, V. M. ‐., & Trojanowski, J. Q. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.012 · Cited by 141 · see citing works
Lin, K.-J., Lin, K.-L., Chen, S., Liou, C., Chuang, Y., Lin, H., & Lin, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215312 · Cited by 141 · see citing works
Dunn, A. R., Stout, K. A., Ozawa, M., Lohr, K. M., Hoffman, C. A., Bernstein, A. I., Li, Y., Wang, M., Sgobio, C., Sastry, N. G., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616892114 · Cited by 138 · see citing works
The Close Encounter Between Alpha-Synuclein and Mitochondria
Vicario, M., Cieri, D., Brini, M., & Calí, T. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00388 · Cited by 132 · see citing works
Hoffmann, A.-C., Minakaki, G., Menges, S., Salvi, R., Savitskiy, S., Kazman, A., Miranda, H. V., Mielenz, D., Klucken, J., Winkler, J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-35811-8 · Cited by 133 · see citing works
Defining α-synuclein species responsible for Parkinson’s disease phenotypes in mice
Froula, J. M., Castellana-Cruz, M., Anabtawi, N. M., Camino, J. D., Chen, S. W., Thrasher, D. R., Freire, J., Yazdi, A. A., Fleming, S., Dobson, C. M., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007743 · Cited by 129 · see citing works
Structural Characteristics of α-Synuclein Oligomers
Cremades, N., Chen, S. W., & Dobson, C. M. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.08.010 · Cited by 118 · see citing works
New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
Zhang, G., Xia, Y. F., Wan, F. J., Ma, K., Guo, X., Kou, L., Yin, S., Han, C., Liu, L., Huang, J., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00370 · Cited by 115 · see citing works
Cellular models of alpha‐synuclein toxicity and aggregation
Delenclos, M., Burgess, J. D., Lamprokostopoulou, A., Outeiro, T. F., Vekrellis, K., & McLean, P. J. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14806 · Cited by 116 · see citing works
Miranda, H. V., Cássio, R., Guedes, L. C., Gomes, M. A., Chegão, A., Miranda, E., Soares, T., Coelho, M. M., Rosa, M. M., Ferreira, J. J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14175-5 · Cited by 111 · see citing works
Alza, N. P., González, P. A. I., Conde, M. A., Uranga, R. M., & Salvador, G. A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00175 · Cited by 111 · see citing works
Volpicelli‐Daley, L. A., Kirik, D., Stoyka, L. E., Standaert, D. G., & Harms, A. S. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13627 · Cited by 110 · see citing works
Alpha Synuclein: Neurodegeneration and Inflammation
Forloni, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065914 · Cited by 111 · see citing works
Imberdis, T., Negri, J. M., Ramalingam, N., Terry-Kantor, E., Ho, G. P. H., Fanning, S., Stirtz, G. L., Kim, T., Levy, O. A., Young‐Pearse, T. L., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903216116 · Cited by 105 · see citing works
Self-citationPathological Functions of LRRK2 in Parkinson’s Disease
Jeong, G. R., & Lee, B. D. (2020) · Cells · doi:10.3390/cells9122565 · Cited by 105 · see citing works
The usual suspects, dopamine and alpha‐synuclein, conspire to cause neurodegeneration
Mor, D. E., Daniels, M. J., & Ischiropoulos, H. (2019) · Movement Disorders · doi:10.1002/mds.27607 · Cited by 103 · see citing works
Transmission of α-synuclein seeds in neurodegenerative disease: recent developments
Karpowicz, R. J., Trojanowski, J. Q., & Lee, V. M. ‐. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0195-z · Cited by 102 · see citing works
Dettmer, U., Ramalingam, N., von Saucken, V. E., Kim, T., Newman, A. J., Terry-Kantor, E., Nuber, S., Ericsson, M., Fanning, S., Bartels, T., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx227 · Cited by 102 · see citing works
Self-citationYu, H., Han, W., Ma, W., & Schulten, K. J. (2015) · The Journal of Chemical Physics · doi:10.1063/1.4936910 · Cited by 99 · see citing works
New insights into cellular α-synuclein homeostasis in health and disease
Dettmer, U., Selkoe, D. J., & Bartels, T. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.07.007 · Cited by 96 · see citing works
Self-citationPrion-like propagation of pathology in Parkinson disease
Volpicelli‐Daley, L. A., & Brundin, P. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63945-5.00017-9 · Cited by 95 · see citing works
Selective vulnerability in α-synucleinopathies
Alegre‐Abarrategui, J., Brimblecombe, K. R., Roberts, R. F., Velentza‐Almpani, E., Tilley, B. S., Bengoa‐Vergniory, N., & Proukakis, C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02010-2 · Cited by 89 · see citing works
Alpha and Beta Synucleins: From Pathophysiology to Clinical Application as Biomarkers
Barba, L., Paoletti, F. P., Bellomo, G., Gaetani, L., Halbgebauer, S., Oeckl, P., Otto, M., & Parnetti, L. (2022) · Movement Disorders · doi:10.1002/mds.28941 · Cited by 88 · see citing works
ɑ‐Synuclein strains and the variable pathologies of synucleinopathies
Peelaerts, W., & Baekelandt, V. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13595 · Cited by 89 · see citing works
Dynamic structural flexibility of α-synuclein
Mor, D. E., Ugras, S. E., Daniels, M. J., & Ischiropoulos, H. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.12.018 · Cited by 82 · see citing works
Genetics of Parkinson’s disease and related disorders
Zhang, P.-L., Chen, Y., Zhang, C.-H., Wang, Y.-X., & Fernandez-Funez, P. (2017) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2017-105047 · Cited by 69 · see citing works
Interaction between Parkin and α-Synuclein in PARK2-Mediated Parkinson’s Disease
Madsen, D. A., Schmidt, S. I., Blaabjerg, M., & Meyer, M. (2021) · Cells · doi:10.3390/cells10020283 · Cited by 85 · see citing works
Minakaki, G., Krainc, D., & Burbulla, L. F. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.580634 · Cited by 83 · see citing works
Gonçalves, S. A., Macedo, D., Raquel, H., Simões, P. D., Giorgini, F., Ramalho, J. S., Barral, D. C., Moita, L. F., & Outeiro, T. F. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005995 · Cited by 80 · see citing works
Finkelstein, D. I., Hare, D. J., Billings, J. L., Sedjahtera, A., Nurjono, M., Arthofer, E., George, S., Culvenor, J. G., Bush, A. I., & Adlard, P. A. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00253 · Cited by 79 · see citing works
The Contribution of α -Synuclein Spreading to Parkinson’s Disease Synaptopathy
Longhena, F., Faustini, G., Missale, C., Pizzi, M., Spano, P., & Bellucci, A. (2017) · Neural Plasticity · doi:10.1155/2017/5012129 · Cited by 81 · see citing works
Giorgi, F. D., Laferrière, F., Zinghirino, F., Faggiani, E., Lends, A., Bertoni, M., Yu, X., Grélard, A., Morvan, E., Habenstein, B., et al. (2020) · Science Advances · doi:10.1126/sciadv.abc4364 · Cited by 80 · see citing works
Duce, J. A., Wong, B. X. W., Durham, H., Devedjian, J.-C., Smith, D. P., & Devos, D. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0186-8 · Cited by 80 · see citing works
The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
Titze-de-Almeida, S. S., Soto‐Sánchez, C., Fernández, E., Koprich, J. B., Brotchie, J. M., & Titze‐de‐Almeida, R. (2020) · Cells · doi:10.3390/cells9040841 · Cited by 76 · see citing works
Αlpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson’s Disease
Bobela, W., Aebischer, P., & Schneider, B. L. (2015) · Biomolecules · doi:10.3390/biom5042675 · Cited by 75 · see citing works
Wu, Y., Chiu, F., Yeh, C.-S., & Kuo, H. (2019) · Open Biology · doi:10.1098/rsob.180177 · Cited by 75 · see citing works
Oiwa, K., Watanabe, S., Onodera, K., Iguchi, Y., Kinoshita, Y., Komine, O., Sobue, A., Okada, Y., Katsuno, M., & Yamanaka, K. (2023) · Science Advances · doi:10.1126/sciadv.adf6895 · Cited by 73 · see citing works
GABA transmission via ATP-dependent K + channels regulates α-synuclein secretion in mouse striatum
Emmanouilidou, E., Minakaki, G., Keramioti, M. V., Xylaki, M., Balafas, E., Chrysanthou‐Piterou, M., Kloukina, I., & Vekrellis, K. (2016) · Brain · doi:10.1093/brain/awv403 · Cited by 76 · see citing works
Subcellular localization of alpha-synuclein aggregates and their interaction with membranes
Colla, E., Miraglia, F., Ricci, A., & Rota, L. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.235013 · Cited by 74 · see citing works
Yue, Q., Li, X., Wu, F., Ji, W., Zhang, Y., Yu, P., Zhang, M., Ma, W., Wang, M., & Mao, L. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202002455 · Cited by 71 · see citing works
Human Pluripotent Stem Cells in Neurodegenerative Diseases: Potentials, Advances and Limitations
Kolagar, T. A., Farzaneh, M., Nikkar, N., & Khoshnam, S. E. (2019) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x14666190823142911 · Cited by 71 · see citing works
Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson’s Disease
Saramowicz, K., Siwecka, N., Galita, G., Kucharska-Lusina, A., Rozpędek‐Kamińska, W., & Majsterek, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010360 · Cited by 76 · see citing works
The Role of Lipids in the Initiation of α-Synuclein Misfolding
Kiechle, M., Grozdanov, V., & Danzer, K. M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.562241 · Cited by 70 · see citing works
Luna, E., & Luk, K. C. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.10.023 · Cited by 65 · see citing works
Salveson, P. J., Spencer, R. K., & Nowick, J. S. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b13261 · Cited by 67 · see citing works
Ottolini, D., Calí, T., Szabó, I., & Brini, M. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0201 · Cited by 63 · see citing works
Nuber, S., Nam, A. Y., Rajsombath, M. M., Cirka, H., Hronowski, X. L., Wang, J., Hodgetts, K. J., Kalinichenko, L. S., Müller, C. P., Lambrecht, V., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25920 · Cited by 63 · see citing works
Self-citationArachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein
Iljina, M., Tosatto, L., Choi, M. L., Sang, J. C., Ye, Y., Hughes, C. D., Bryant, C. E., Gandhi, S., & Klenerman, D. (2016) · Scientific Reports · doi:10.1038/srep33928 · Cited by 62 · see citing works
Long, H., Zheng, W., Liu, Y., Sun, Y., Zhao, K., Liu, Z., Xia, W., Lv, S., Liu, Z., Li, D., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2012435118 · Cited by 60 · see citing works
Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits
Larson, M. E., Greimel, S. J., Amar, F., LaCroix, M., Boyle, G., Sherman, M. A., Schley, H., Miel, C., Schneider, J. A., Kayed, R., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704698114 · Cited by 61 · see citing works
Kayed, R., Dettmer, U., & Lesné, S. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-201965 · Cited by 62 · see citing works
Self-citationTherapeutic importance of hydrogen sulfide in age-associated neurodegenerative diseases
Jeong, N., Jung, J., & Tabassum, R. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.266911 · Cited by 61 · see citing works
Kim, T., & Vemuganti, R. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17694186 · Cited by 61 · see citing works
The interaction of α-synuclein and Tau: A molecular conspiracy in neurodegeneration?
Xu, Y., Uronen, R., & Huttunen, H. J. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.05.005 · Cited by 61 · see citing works
Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders
Erskine, D., Koss, D. J., Korolchuk, V. I., Outeiro, T. F., Attems, J., & McKeith, I. G. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02266-7 · Cited by 58 · see citing works
Anandhan, A., Lei, S., Levytskyy, R. M., Pappa, A., Panayiotidis, M. I., Cerny, R. L., Khalimonchuk, O., Powers, R., & Franco, R. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9906-2 · Cited by 58 · see citing works
Mutations in LRRK2 impair NF-κB pathway in iPSC-derived neurons
de Maturana, R. L., Lang, V., Zubiarrain, A., Sousa, A., Vázquez, N., Gorostidi, A., Benitez, J. A., de Munaín, A. L., Rodríguez, M. S., & Sánchez‐Pernaute, R. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0761-x · Cited by 57 · see citing works
Gilmozzi, V., Gentile, G., Rueda, M. P. C., Hicks, A. A., Pramstaller, P. P., Zanon, A., Lévesque, M., & Pichler, I. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.578993 · Cited by 56 · see citing works
Vesicle trafficking and lipid metabolism in synucleinopathy
Fanning, S., Selkoe, D. J., & Dettmer, U. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02177-z · Cited by 55 · see citing works
Self-citationDuffy, M. F., Collier, T. J., Patterson, J. R., Kemp, C. J., Fischer, D. L., Stoll, A. C., & Sortwell, C. E. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00621 · Cited by 51 · see citing works
Hassanzadeh, K., Liu, J., Maddila, S. C., & Mouradian, M. M. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.001111 · Cited by 53 · see citing works
The Membrane Interactions of Synuclein: Physiology and Pathology
Runwal, G., & Edwards, R. H. (2021) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-031920-092547 · Cited by 53 · see citing works
Stykel, M. G., Humphries, K. M., Kamski‐Hennekam, E. R., Buchner-Duby, B., Porte-Trachsel, N., Ryan, T. L., Coackley, C. L., Bamm, V. V., Harauz, G., & Ryan, S. D. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109099 · Cited by 53 · see citing works
Fonseca‐Ornelas, L., Viennet, T., Rovere, M., Jiang, H., Liu, L., Nuber, S., Ericsson, M., Arthanari, H., & Selkoe, D. J. (2020) · Cell Reports · doi:10.1016/j.celrep.2021.109333 · Cited by 50 · see citing works
Self-citationGBA1 Variants and Parkinson’s Disease: Paving the Way for Targeted Therapy
Huh, Y. E., Usnich, T., Scherzer, C. R., Klein, C., & Chung, S. J. (2023) · Journal of Movement Disorders · doi:10.14802/jmd.23023 · Cited by 51 · see citing works
Mohankumar, A., Shanmugam, G., Kalaiselvi, D., Levenson, C., Nivitha, S., Thiruppathi, G., & Sundararaj, P. (2018) · RSC Advances · doi:10.1039/c8ra05195j · Cited by 51 · see citing works
Bell, R., & Vendruscolo, M. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.661117 · Cited by 52 · see citing works
Synucleinopathies: common features and hippocampal manifestations
Yang, W., & Yu, S. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2411-y · Cited by 49 · see citing works
Tuning the immune system by nanoparticle–biomolecular corona
Palmieri, V., & Caracciolo, G. (2022) · Nanoscale Advances · doi:10.1039/d2na00290f · Cited by 50 · see citing works
- Authors
- Dettmer, U., Newman, A. J., Soldner, F., Luth, E. S., Kim, N. C., von Saucken, V. E., Sanderson, J. B., Jaenisch, R., Bartels, T., & Selkoe, D.
- Affiliations
- Brigham and Women's Hospital (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Selkoe, Dennis
- ORCID
- Venue
- Nature Communications
- Published
- 2015-06-16
- Volume
- 6
- Issue
- 1
- Pages
- 7314-7314
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4490410
- OpenAlex
- W1886318170
- Cited by
- 317
- References
- 56
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 24 · 2023: 22 · 2022: 19 · 2021: 32 · 2020: 35 · 2019: 43 · 2018: 29 · 2017: 33 · 2016: 31 · 2015: 11
- FWCI
- 24.43
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-07-30)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Parkinson's Disease Foundation
- National Institutes of Health (HD 045022, R01-NS083845, NS083845)
- Fidelity Biosciences
- National Cancer Institute (5R37 CA84198, R37CA084198)
- National Institute of Neurological Disorders and Stroke (RF1NS083845, R01NS083845)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD045022, HD045022, R37HD045022)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, Parkinson's disease, missense mutations, A53T mutation, E46K mutation, tetramer, monomers, protein aggregation, neurotoxicity, tetramer stabilization, disease initiation, human brain
- MeSH terms
- Animals, Brain, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Neurons, Parkinson Disease, Immunoblotting, Rats, Sprague-Dawley, Mutation, Missense, Protein Structure, Quaternary, Mice, Rats, alpha-Synuclein, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
