The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
A Hydrophobic Stretch of 12 Amino Acid Residues in the Middle of α-Synuclein Is Essential for Filament Assembly
Open accessAbstract
Neuronal and oligodendrocytic aggregates of fibrillar alpha-synuclein define several diseases of the nervous system. It is likely that these inclusions impair vital metabolic processes and compromise viability of affected cells. Here, we report that a 12-amino acid stretch ((71)VTGVTAVAQKTV(82)) in the middle of the hydrophobic domain of human alpha-synuclein is necessary and sufficient for its fibrillization based on the following observations: 1) human beta-synuclein is highly homologous to alpha-synuclein but lacks these 12 residues, and it does not assemble into filaments in vitro; 2) the rate of alpha-synuclein polymerization in vitro decreases after the introduction of a single charged amino acid within these 12 residues, and a deletion within this region abrogates assembly; 3) this stretch of 12 amino acids appears to form the core of alpha-synuclein filaments, because it is resistant to proteolytic digestion in alpha-synuclein filaments; and 4) synthetic peptides corresponding to this 12-amino acid stretch self-polymerize to form filaments, and these peptides promote fibrillization of full-length human alpha-synuclein in vitro. Thus, we have identified key sequence elements necessary for the assembly of human alpha-synuclein into filaments, and these elements may be exploited as targets for the design of drugs that inhibit alpha-synuclein fibrillization and might arrest disease progression.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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 the citing paper
“Introducing hydrophilic point mutations within the NAC significantly reduces the oligomerization and fibrillation potential of αSyn”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [116]
Citations
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
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
Self-citationSpillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 2,868
(1998) · Europe PMC (PubMed Central) · Cited by 1,594
Self-citationConway, K. A., Harper, J. D., & Lansbury, P. T. (1998) · Nature Medicine · doi:10.1038/3311 · Cited by 1,520
Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease.
Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D. A., Kondo, J. D. M., Ihara, Y., & Saitoh, T. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11282 · Cited by 1,469
Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., Rohan de Silva, H. A., Kittel, A., & Saitoh, T. (1995) · Neuron · doi:10.1016/0896-6273(95)90302-x · Cited by 1,316
Identification of two distinct synucleins from human brain
Jakes, R., Spillantini, M. G., & Goedert, M. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00395-5 · Cited by 1,080
Spillantini, M. G., Crowther, R. A., Jakes, R., Cairns, N. J., Lantos, P. L., & Goedert, M. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00504-7 · Cited by 1,052
George, J. M., Jin, H., Woods, W. S., & Clayton, D. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90040-3 · Cited by 844
Flagged first, then by citations
Research works printed but not linked: 3
- Baba, 1998, Am. J. Pathol., 152, 879
- Takeda, 1998, Am. J. Pathol., 152, 367
- Masliah, 1996, Am. J. Pathol., 148, 201
Cited by
Sorted by citations
Items 901–1,000 of 1,000
Martins, G. F., Rocha, C., & Galamba, N. (2025) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5c05501 · Cited by 1
Familial mutations modulate α‐synuclein interactions with key neuronal membrane lipids
Ali, A., Matveyenka, M., & Kurouski, D. (2025) · FEBS Journal · doi:10.1111/febs.70363 · Cited by 1
Inertial Agitation in an NMR Magnet: Real-Time Monitoring of Protein Aggregation at High Resolution
Lee, J., Jung, S., Yu, S., Park, S. H., Kim, N., & Lee, J. H. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c16918 · Cited by 1
Effect of sequence variations on the phase behavior of a functional IDP fragment
Chakraborty, S., Mishra, N., & Biswas, M. (2026) · The Journal of Chemical Physics · doi:10.1063/5.0299964 · Cited by 1
Shi, Y., Wang, H., Chen, J., Ren, J., Sun, X., Qu, M., Zhao, T., Han, C., Yuan, J., Meng, F., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05686-2 · Cited by 1
Xia, C. A., Tsai, H., Garcia, S. D., Liu, S., Matzeu, A., Salarian, M., Bruinzeel, W., & Szardenings, A. K. (2026) · npj Imaging · doi:10.1038/s44303-026-00138-x · Cited by 1
Multiscale Insights into the Ionic‐Strength Dependence of α‐Synuclein Liquid–Liquid Phase Separation
Chen, C., Yan, Z., Ma, Y., & Ding, H. (2026) · Macromolecular Rapid Communications · doi:10.1002/marc.202500966 · Cited by 1
Ghahari, A., Alikhanian, A., Solaei, F. A., Fattahi, A., Hourfar, H., Schallmey, A., Mohammadi, M., & Morshedi, D. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02534-9 · Cited by 1
Alfaidi, M., Wenger, L. M. D., Szebényi, K., Stoker, T. B., He, X., Fazal, S. V., Šebestíková, J., Jassim, A., Gilbertson, R. J., Garza, R., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-10134-x · Cited by 1
Structural biology of alpha-synuclein amyloid filaments: Implications in synucleinopathies
Gonçalves, P. D. C., Fernández, I., & Fernández, C. O. (2026) · Journal of Parkinson s Disease · doi:10.1177/1877718x261461375 · Cited by 1
Phase separation and protein aggregation in neurodegenerative diseases
Seiglière, H. D. L., Letourneur, Æ., Ichas, F., & Giorgi, F. D. (2026) · Biophysical Chemistry · doi:10.1016/j.bpc.2026.107678 · Cited by 1
Sun, F., Anantharam, V., Jin, H., Zhang, D., Kanthasamy, A., & Kanthasamy, A. G. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374028-1.00036-1 · Cited by 1
Pathogenesis of neurodegenerative diseases via templated recruitment
Guo, J. (2013) · ScholarlyCommons (University of Pennsylvania) · Cited by 1
Alpha-Synuclein Interactions with Membranes
Pirc, K., & Poklar, N. (2011) · InTech eBooks · doi:10.5772/16816 · Cited by 1
Amyloid Polymorphism of α-Synuclein Induced by Active Firefly Luciferase
Yang, J. E., Hong, J. W., Kim, J., & Paik, S. R. (2014) · Bulletin of the Korean Chemical Society · doi:10.5012/bkcs.2014.35.2.425 · Cited by 1
Protein seeding in Alzheimer’s disease and Parkinson’s disease: Similarities and differences
Ibrahim, T. (2014) · World Journal of Neurology · doi:10.5316/wjn.v4.i4.23 · Cited by 1
Volpicelli‐Daley, L. A., & Standaert, D. G. (2016) · Movement Disorders · doi:10.1002/mds.26465 · Cited by 1
Large Unilamellar Vesicles of Phosphatidic Acid Reduce the Toxicity of α-Synuclein Fibrils
Ali, A., Holman, A. P., Rodriguez, A., Zhaliazka, K., Osborne, L., & Kurouski, D. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c01012 · Cited by 1
Alpha-synuclein as a Molecular Marker for the Diagnosis of Neurological Disorders
Bagree, G., Silva, O. D., Liyanage, P. D., Mahasivam, S., Bansal, V., & Ramanathan, R. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837673216-00286 · Cited by 1
Therapeutic Strategies in Neurodegenerative Diseases
Eid, A. M., Faridar, A., & Appel, S. H. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_39 · Cited by 1
CFS Biomarkers in Parkinson’s Disease
Parnetti, L., Castrioto, A., De, C., Chiasserini, D., Tambasco, N., Rossi, A., Balducci, C., Beccari, T., & Calabresi, P. (2011) · InTech eBooks · doi:10.5772/16666 · Cited by 1
Amyloidogenic Protein of α-Synuclein
Yang, J. E., & Paik, S. R. (2013) · Hanyang Medical Reviews · doi:10.7599/hmr.2013.33.2.123 · Cited by 1
Hyun, M., & Lee, S. (2009) · Experimental Neurobiology · doi:10.5607/en.2009.18.1.19 · Cited by 1
Molecular Biology of Dementia with Lewy Bodies
Hasegawa, M. (2016) · Springer eBooks · doi:10.1007/978-4-431-55948-1_4 · Cited by 1
Amyloidogenic Pattern Prediction of HIV-1 Proteins
Sneha, P., Balaji, S., & Shapshak, P. (2017) · Springer eBooks · doi:10.1007/978-1-4939-7290-6_33 · Cited by 1
Insights into the misfolding of ‒synuclein in the presence of metal ions: a simulation study
Pagadala, N. S. (2018) · MOJ Drug Design Development & Therapy · doi:10.15406/mojddt.2018.02.00030 · Cited by 1
Biomarker detection of Parkinson’s disease: therapy and treatment using nanomaterials
Nanda, R., Panda, P., & Mishra, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817923-9.00017-1 · Cited by 1
Chau, E., & Kim, J. R. (2021) · Biochemical Engineering Journal · doi:10.1016/j.bej.2021.108292 · Cited by 1
Muñoz, A. R., Fernández-Pérez, E. J., Olivos, N., Burgos, C. F., Boopathi, S., Armijo‐Weingart, L., Pacheco, C. R., González, W., & Aguayo, L. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413253 · Cited by 1
Structural and Functional Insights into α‐Synuclein–Lipid Interactions
Stöckl, M. T., van Rooijen, B. D., Claessens, M. M. A. E., & Subramaniam, V. (2011) · Wiley eBooks · doi:10.1002/9783527634323.ch2 · Cited by 1
Tanik, S. A. (2013) · Scholarly Commons (University of Pennsylvania) · Cited by 1
Vlad, C. (2011) · KOPS (University of Konstanz) · Cited by 1
Biophysical characterization of alpha-synuclein aggregates : Parkinson's disease at the nanoscale
van Raaij, M. E. (2008) · doi:10.3990/1.9789036527477 · Cited by 1
Neurodegenerative α-Synucleinopathies
Goedert, M., & Spillantini, M. G. (2005) · Humana Press eBooks · doi:10.1385/1-59259-834-x:077 · Cited by 1
Alpha-synuclein and the multiple hit hypothesis of Parkinson's disease
Feng, L. (2012) · DigitalGeorgetown (Georgetown University Library) · Cited by 1
Mammeri, H. (2006) · Cited by 1
The use of cell-free systems to characterize parkinson's disease-related gene products
Rochet, J., & Schieler, J. L. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374028-1.00043-9 · Cited by 1
Apetri, M. M. (2006) · OhioLink ETD Center (Ohio Library and Information Network) · Cited by 1
Aggregation and conformation of alpha-synuclein: effects of ligand binding and phosphomimetics
Paskins, A. R. (2017) · Sheffield Hallam University · doi:10.7190/shu-thesis-00071 · Cited by 1
Conformational changes and the self-assembly of alpha-synuclein
Mason, R. J. A. (2018) · Sheffield Hallam University · doi:10.7190/shu-thesis-00151 · Cited by 1
Exceptional aggregation propensity of amino acids in polyglutamine amino-acid-homopolymerPreprint
Mishra, R., & Thakur, A. K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.09.194753 · Cited by 1
Choi, S. G., Duvernay, J. B., Bahrami, A., Tittle, T., Sani, S., Kordower, J. H., Muller, S., & Killinger, B. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.22.649861 · Cited by 2
Theint, A. T., Cazares, N., Zhang, S., Zhang, N., Mosley, R., Ishida, K., Higuchi, M., Peng, C., & Zeiger, W. (2026) · npj Parkinson s Disease · doi:10.1101/2025.07.31.668024 · Cited by 1
α-Synuclein, CSPα, SNAREs and Neuroprotection in vivo
Chandra, S. S., & Südhof, T. C. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374028-1.00022-1
Molecular Biology of α-Synuclein
Rieß, O., Krüger, R., Kobayashi, H., Holzmann, C., Hattori, N., & Mizuno, Y. (2002) · Advances in behavioral biology · doi:10.1007/978-0-306-47593-1_85
Valastyan, J. S. (2013) · DSpace@MIT (Massachusetts Institute of Technology)
Regional lysosomal malfunction underlies the selectivity of alpha-synuclein neurodegeneration
Malkus, K. A. (2011) · Scholarly Commons (University of Pennsylvania)
Effects of Aggregated Alpha-Synuclein on Cultured Neuronal Cells
Freeman, D. W. (2015) · Loyola eCommons (Loyola University of Chicago)
Synucleins in the midbrain dopaminergic system : the role in health and disease
Connor‐Robson, N. (2013) · ORCA Online Research @Cardiff (Cardiff University)
The role of alpha synuclein in Parkinson’s disease
Moualla, D. (2011) · The University of Bath Online Publications Store (The University of Bath)
Behavioural analysis of transgenic mice overexpressing gamma-synuclein
Salem, H. (2011) · ORCA Online Research @Cardiff (Cardiff University)
Treating Oxidative Neural Injury: Methionine Sulfoxide Reductase Therapy for Parkinson’s Disease
Wassef, R., Heinemann, S. H., & Hoshi, T. (2009) · Contemporary clinical neuroscience · doi:10.1007/978-1-60327-342-8_12
Valtierra, S. (2009) · Eukaryon
Savolainen, M. H. (2015) · Työväentutkimus Vuosikirja
Utilizing Galectin 3 as a Marker of Ruptured Vesicles In Vivo
London, J. (2015) · Loyola eCommons (Loyola University of Chicago)
Role of Aberrant α-Synuclein–Membrane Interactions in Parkinson’s Disease
Griggs, A. M., Ysselstein, D., & Rochet, J. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-394431-3.00039-0
Non-Canonical Amino Acids as Minimal Tags for Investigating Protein Organization and Turnover
Gebura-Vreja, I.-C. (2016) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-5450
Détection et caractérisation de peptides obliques au sein des protéines amyloïdogéniques
Crowet, J., Brasseur, R., & Lins, L. (2008)
Les marqueurs biologiques de l'atrophie multisystématisée
Laurens, B. (2014) · HAL
The role of alpha-synuclein phosphorylation in synucleinopathies
Basso, E. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Extracellular vesicle release of α-Synuclein is mediated by SUMOylation
Kunadt, M. (2015) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-5371
Amyloid State of Proteins in Human Disease
Huang, L., & Huang, K. (2015) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0024459
MODULATION OF ALPHA-SYNUCLEIN PROTEIN FOLDING BY A MARINE-SOURCED EXTRACT
Giffin, J. C., Richards, R. C., Craft, C., Jahan, N., Chopin, T., Szemerda, M., MacKinnon, S. L., & Ewart, K. V. (2013) · DalSpace (Dalhousie University)
Etude expérimentale du peptide oblique de l'α-synucléine
Gembloux, A. D. (2004)
pH- and temperature-dependent mechanisms of non-native aggregation of anti-CD40 IgG1
Wu, H. (2024) · Library, Museums and Press - UDSpace (University of Delaware) · doi:10.58088/83s2-4831
The Neuroprotective Role of Micronutrients in Parkinson’s Disease
Malkus, K. A., Tsika, E., & Ischiropoulos, H. (2009) · doi:10.1201/9781420073522-7
Basic algorithms of bioinformatics
King, M. R., & Mody, N. A. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511780936.010
Pathogenic mechanisms in multiple system atrophy: a study of oligodendroglial pathology
Asi, Y. T. (2014) · UCL Discovery (University College London)
Synuclein misfolding as a therapeutic target
Peelaerts, W., & Outeiro, T. F. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805120-7.00002-6
Langston, J. W., Golbe, L. I., & Lee, S. (2003) · Elsevier eBooks · doi:10.1016/b978-012566652-7/50029-0
Panda, S., & Guttula, P. K. (2017) · International Journal of Pharma and Bio Sciences · doi:10.22376/ijpbs.2017.8.4.b330-337
Approach Towards The Development Of Novel Disease Modifying Therapeutics For Parkinson's Disease
Luo, D. (2017) · Human Biology
Datta, I., & Ganapathy, K. (2017) · InTech eBooks · doi:10.5772/intechopen.70405
Interactions of the disordered TPPP/p25 with physiological and pathological partners
Szunyogh, S. (2017) · Eötvös Loránd Tudományegyetem · doi:10.15476/elte.2016.188
Masaracchia, C. (2018) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7134
The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes
Sackmann, V. (2019) · Linköping University medical dissertations · doi:10.3384/diss.diva-160949 · Cited by 1
Brodie, N. I. (2020) · Journal of Proteomics
Recapitulating Parkinson’s disease pathology in a three-dimensional neural cell culture model
Taylor-Whiteley, T. R. (2019) · Sheffield Hallam University · doi:10.7190/shu-thesis-00321
CSF Biomarkers in Parkinson's disease
Parnetti, L., Castrioto, A., Carlo, C. D., Chiasserini, D., Tambasco, N., Rossi, A., Michiara, M., Beccari, T., & Calabresi, P. (2011)
Mecanismes de toxicitat de la dopamina en cèl·lules de neuroblastoma humà SH-SY5Y
Xavier, P. G. (2008) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Merino, P. (2019) · Wiley eBooks · doi:10.1002/9783527813421.ch9
The Neuroprotective Role of Micronutrients in Parkinson’s Disease
Tsika, E., Ischiropoulos, H., & Malkus, K. A. (2009) · Oxidative stress and disease · doi:10.1201/9781420073522.ch2
Fasano, A. A., & Breen, D. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733203098.793545981
Faculty Opinions recommendation of Cryo-EM structure of alpha-synuclein fibrils.
Scheres, S. H. W. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733570511.793550310
The Effects of Stress on Lewy Pathology in Dopamine NeuronsPreprint
Zhang, X., Zhao, M., zhang, L., Geng, D., Huang, M., Li, D., gao, Y., Zhang, F., Zhan, C., Yuan, K., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4098912
Dissolution of amyloid aggregates by direct addition of alkali halides
Takekiyo, T., Yamada, N., Amo, T., Nakazawa, C. T., Asano, A., Ichimura, T., Katō, M., & Yoshimura, Y. (2022) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2022.120849
Das, D., & Mattaparthi, V. S. K. (2024) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2024.2310788
Mughal, K. A., Khan, A. Q., Sarwar, A., Mahmood, R., & Abbasi, A. A. (2024) · Biologia · doi:10.1007/s11756-024-01713-6
Metadata
- Authors
- Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Lee, Virginia M.-Y.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 276
- Issue
- 4
- Pages
- 2380-2386
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2166789153
- Cited by
- 1,080
- References
- 36
- Citations by year
- 2026: 33 · 2025: 60 · 2024: 77 · 2023: 58 · 2022: 78 · 2021: 59 · 2020: 65 · 2019: 51 · 2018: 57 · 2017: 51 · 2016: 36 · 2015: 36 · 2014: 39 · 2013: 32 · 2012: 36
- FWCI
- 21.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, fibrillization, filament assembly, hydrophobic domains, beta-synuclein, protease resistance, amyloid fibrils, neurodegenerative diseases
- MeSH terms
- Amino Acid Sequence, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Nervous System Diseases, Peptide Fragments, Protein Binding, Protein Conformation, Recombinant Proteins, Synucleins, alpha-Synuclein, beta-Synuclein
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