The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The Impact of the E46K Mutation on the Properties of α-Synuclein in Its Monomeric and Oligomeric States
Open accessAbstract
The third and most recently identified Parkinson's disease-linked variant of the neuronal protein alpha-synuclein to be identified (E46K) results in widespread brain pathology and early onset Parkinson symptoms (Zarranz et al. (2004) Ann. Neurol. 55, 164-173). Herein, we present biochemical and biophysical characterization of E46K alpha-synuclein in various states of aggregation. Circular dichroism and nuclear magnetic resonance spectroscopy illustrate that the E46K mutation results in subtle changes in the conformation of the monomeric protein both free in solution and in the presence of SDS micelles. However, it does not alter the overall helical propensity of the protein in the presence of phospholipids. E46K alpha-synuclein formed insoluble fibrils in vitro more rapidly than the wild type protein, and electron microscopy revealed that E46K alpha-synuclein fibrils possess a typical amyloid ultrastructure. E46K alpha-synuclein protofibrils, soluble aggregates that form during the transition from the monomeric form to the fibrillar form of alpha-synuclein, were characterized by electron microscopy and gel filtration and were found to include annular species. The unique ability of a subfraction of E46K and wild type alpha-synuclein protofibrils containing porelike species to permeabilize lipid vesicles was demonstrated in vitro using a real-time chromatographic method. In contrast to simplistic expectations, the total amount of protofibrils and the amount of permeabilizing activity per mole protein in the protofibril fraction were reduced by the E46K mutation. These results suggest that if the porelike activity of alpha-synuclein is important for neurotoxicity, there must be factors in the neuronal cytoplasm that reverse the trends in the intrinsic properties of E46K versus WT alpha-synuclein that are observed in vitro.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
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
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
Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., Ryan, A., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)80886-7 · Cited by 1,722
Clearance of α-Synuclein Oligomeric Intermediates via the Lysosomal Degradation Pathway
Lee, H.-J., Khoshaghideh, F., Patel, S., & Lee, S.-J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3809-03.2004 · Cited by 445
Cited by
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Mitochondrial dysfunction and oxidative stress in Parkinson's disease
Subramaniam, S. R., & Chesselet, M.-F. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.004 · Cited by 913
Oxidative Stress and Neurotoxicity
Sayre, L. M., Perry, G., & Smith, M. A. (2008) · Chemical Research in Toxicology · doi:10.1021/tx700210j · Cited by 867
α-Synuclein misfolding and Parkinson's disease
Breydo, L., Wu, J. W., & Uversky, V. N. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.002 · Cited by 657
Cell Biology and Pathophysiology of α-Synuclein
Burré, J., Sharma, M., & Südhof, T. C. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024091 · Cited by 579
Karpinar, D. P., Balija, M. B. G., Kügler, S., Opazo, F., Rezaei‐Ghaleh, N., Wender, N., Kim, H., Taschenberger, G., Falkenburger, B. H., Heise, H., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.257 · Cited by 432
Dementia with Lewy bodies: an update and outlook
Outeiro, T. F., Koss, D. J., Erskine, D., Walker, L., Kurzawa-Akanbi, M., Burn, D., Donaghy, P., Morris, C., Taylor, J.-P., Thomas, A., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0306-8 · Cited by 381
Freeman, D., Cedillos, R., Choyke, S., Lukic, Z., McGuire, K., Marvin, S., Burrage, A. M., Sudholt, S., Rana, A., O'Connor, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062143 · Cited by 289
Hoenen, C., Gustin, A., Birck, C., Kirchmeyer, M., Beaume, N., Felten, P., Grandbarbe, L., Heuschling, P., & Heurtaux, T. (2016) · PLOS ONE · doi:10.1371/journal.pone.0162717 · Cited by 159
APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid
Zhao, N., Attrebi, O. N., Ren, Y., Qiao, W., Sonustun, B., Martens, Y. A., Meneses, A. D., Li, F., Shue, F., Zheng, J., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay1809 · Cited by 156
Vulnerability of mesostriatal dopaminergic neurons in Parkinson’s disease
González-Hernández, T. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00140 · Cited by 65
Kang, L., Wu, K.-P., Vendruscolo, M., & Baum, J. (2011) · Journal of the American Chemical Society · doi:10.1021/ja203979j · Cited by 65
Metadata
- Authors
- Fredenburg, R. A., Rospigliosi, C., Meray, R. K., Kessler, J. C., Lashuel, H. A., Eliezer, D., & Lansbury, P. T.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-05-26
- Volume
- 46
- Issue
- 24
- Pages
- 7107-7118
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2168076805
- Cited by
- 227
- References
- 5
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- green
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
