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Reversible Inhibition of α-Synuclein Fibrillization by Dopaminochrome-mediated Conformational Alterations
Open accessAbstract
Previous studies demonstrated that alpha-synuclein (alpha-syn) fibrillization is inhibited by dopamine, and studies to understand the molecular basis of this process were conducted (Conway, K. A., Rochet, J. C., Bieganski, R. M., and Lansbury, P. T., Jr. (2001) Science 294, 1346-1349). Dopamine inhibition of alpha-syn fibrillization generated exclusively spherical oligomers that depended on dopamine autoxidation but not alpha-syn oxidation, because mutagenesis of Met, His, and Tyr residues in alpha-syn did not abrogate this inhibition. However, truncation of alpha-syn at residue 125 restored the ability of alpha-syn to fibrillize in the presence of dopamine. Mutagenesis and competition studies with specific synthetic peptides identified alpha-syn residues 125-129 (i.e. YEMPS) as an important region in the dopamine-induced inhibition of alpha-syn fibrillization. Significantly, the dopamine oxidation product dopaminochrome was identified as a specific inhibitor of alpha-syn fibrillization. Dopaminochrome promotes the formation of spherical oligomers by inducing conformational changes, as these oligomers regained the ability to fibrillize by simple denaturation/renaturation. Taken together, these data indicate that dopamine inhibits alpha-syn fibrillization by inducing structural changes in alpha-syn that can occur through the interaction of dopaminochrome with the 125YEMPS129 motif of alpha-syn. These results suggest that the dopamine autoxidation can prevent alpha-syn fibrillization in dopaminergic neurons through a novel mechanism. Thus, decreased dopamine levels in substantia nigra neurons might promote alpha-syn aggregation in Parkinson's disease.
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“Aminochrome is a highly reactive molecule capable of forming adducts with α-synuclein and ROS such as superoxide radical anion and depleting NADPH (Norris et al. 2005).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Norris et al. 2005
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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
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
Lang, A. E., & Lozano, A. M. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810083391506 · Cited by 2,072
The substantia nigra of the human brain
Damier, P., Hirsch, É. C., Agid, Y., & Graybiel, A. M. (1999) · Brain · doi:10.1093/brain/122.8.1437 · Cited by 1,827
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
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 1,622
(1998) · Europe PMC (PubMed Central) · Cited by 1,594
Self-citationGiasson, B. I., Duda, J. E., Murray, I. V. J., Chen, Q., Souza, J. M., Hurtig, H. I., Ischiropoulos, H., Trojanowski, J. Q., & Lee, V. M. ‐. (2000) · Science · doi:10.1126/science.290.5493.985 · Cited by 1,567
Self-citationConway, K. A., Lee, S., Rochet, J., Ding, T. T., Williamson, R. E., & Lansbury, P. T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.571 · Cited by 1,559
Neuropathology of Parkinson's Disease
Forno, L. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199603000-00001 · Cited by 1,556
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
Conway, K. A., Harper, J. D., & Lansbury, P. T. (1998) · Nature Medicine · doi:10.1038/3311 · Cited by 1,520
Alpha-synuclein and neurodegenerative diseases
Goedert, M. (2001) · Nature reviews. Neuroscience · doi:10.1038/35081564 · Cited by 1,428
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
Neuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-Synuclein
Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00682-7 · Cited by 1,266
Self-citationKinetic Stabilization of the α-Synuclein Protofibril by a Dopamine-α-Synuclein Adduct
Conway, K. A., Rochet, J.-C., Bieganski, R. M., & Lansbury, P. T. (2001) · Science · doi:10.1126/science.1063522 · Cited by 1,127
Eliezer, D., Kutluay, E., Bussell, R., & Browne, G. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4538 · Cited by 1,110
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
Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008919200 · Cited by 1,080
Self-citationSpillantini, 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
Murphy, D. D., Rueter, S. M., Trojanowski, J. Q., & Lee, V. M. ‐. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-09-03214.2000 · Cited by 927
Self-citationCabin, D. E., Shimazu, K., Murphy, D., Cole, N. B., Gottschalk, W., McIlwain, K. L., Orrison, B., Chen, A., Ellis, C. E., Paylor, R., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08797.2002 · Cited by 865
George, J. M., Jin, H., Woods, W. S., & Clayton, D. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90040-3 · Cited by 844
Lee, M. K., Stirling, W., Xu, Y., Xu, X., Qui, D., Mandir, A. S., Dawson, T. M., Copeland, N. G., Jenkins, N. A., & Price, D. L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132197599 · Cited by 824
Conway, K. A., Harper, J. D., & Lansbury, P. T. (2000) · Biochemistry · doi:10.1021/bi991447r · Cited by 786
Xu, J., Kao, S., Lee, F. J. S., Song, W., Jin, L., & Yankner, B. A. (2002) · Nature Medicine · doi:10.1038/nm0602-600 · Cited by 768
Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation
Serpell, L. C., Berriman, J. A., Jakes, R., Goedert, M., & Crowther, R. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4897 · Cited by 755
Tu, P., Galvin, J. E., Baba, M., Giasson, B., Tomita, T., Leight, S., Nakajo, S., Iwatsubo, T., Trojanowski, J. Q., & Lee, V. M. ‐. (1998) · Annals of Neurology · doi:10.1002/ana.410440324 · Cited by 686
Self-citationGiasson, B. I., Uryu, K., Trojanowski, J. Q., & Lee, V. M. ‐. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7619 · Cited by 510
Self-citationLee, F. J. S., Liu, F., Pristupa, Z. B., & Niznik, H. B. (2001) · The FASEB Journal · doi:10.1096/fj.00-0334com · Cited by 463
Induction of α-Synuclein Aggregation by Intracellular Nitrative Insult
Paxinou, E., Chen, Q., Weisse, M., Giasson, B. I., Norris, E. H., Rueter, S. M., Trojanowski, J. Q., Lee, V. M. ‐., & Ischiropoulos, H. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08053.2001 · Cited by 440
Self-citationSynthetic filaments assembled from C‐terminally truncated α‐synuclein
Crowther, R. A., Jakes, R., Spillantini, M. G., & Goedert, M. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01146-6 · Cited by 421
Kuzuhara, S., Mori, H., Izumiyama, N., Yoshimura, M., & Ihara, Y. (1988) · Acta Neuropathologica · doi:10.1007/bf00687787 · Cited by 409
Pakkenberg, B., Møller, A., Gundersen, H. J. G., Dam, A. M., & Pakkenberg, H. (1991) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.54.1.30 · Cited by 408
Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders.
Takeda, A., Mallory, M. E., Sundsmo, M. P., Honer, W. G., Hansen, L. A., & Masliah, E. (1998) · Europe PMC (PubMed Central) · Cited by 403
Pathology and Biology of the Lewy Body
Pollanen, M. S., Dickson, D. W., & Bergeron, C. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199305000-00001 · Cited by 396
Irizarry, M. C., Growdon, W., Gómez‐Isla, T., Newell, K. L., George, J. M., Clayton, D. F., & Hyman, B. T. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199804000-00005 · Cited by 394
Role of α-Synuclein Carboxy-Terminus on Fibril Formation in Vitro
Murray, I. V. J., Giasson, B. I., Quinn, S. M., Koppaka, V., Axelsen, P. H., Ischiropoulos, H., Trojanowski, J. Q., & Lee, V. M. ‐. (2003) · Biochemistry · doi:10.1021/bi027363r · Cited by 372
Self-citationNovel antibodies to synuclein show abundant striatal pathology in Lewy body diseases
Duda, J. E., Giasson, B. I., Mabon, M. E., Lee, V. M. ‐., & Trojanowski, J. Q. (2002) · Annals of Neurology · doi:10.1002/ana.10279 · Cited by 322
Self-citationGai, W. P., Yuan, H. X., Li, X. Q., Power, J. T. H., Blumbergs, P. C., & Jensen, P. H. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7527 · Cited by 272
Neuropathology of synuclein aggregates
Duda, J. E., Lee, V. M. ‐., & Trojanowski, J. Q. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000715)61:2 · Cited by 263
Li, J., Zhu, M., Manning-Bog, A., Monte, D. A. D., & Fink, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0770fje · Cited by 259
Attenuation of dopamine transporter activity by α-synuclein
Wersinger, C., & Sidhu, A. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00097-1 · Cited by 197
Norris, E. H., Giasson, B. I., Ischiropoulos, H., & Lee, V. M. ‐. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212436200 · Cited by 182
Self-citationCrowther, R. A., Daniel, S. E., & Goedert, M. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01440-3 · Cited by 154
A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114
Crystal, A., Giasson, B. I., Crowe, A., Kung, M., Zhuang, Z., Trojanowski, J. Q., & Lee, V. M. ‐. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01949.x · Cited by 138
Self-citationKosaka, K., & Iseki, E. (1996) · Current Opinion in Neurology · doi:10.1097/00019052-199608000-00005 · Cited by 37
Ed, L., & Fahn, S. (1996) · PubMed · Cited by 13
Goodrum (2000) · doi:10.1002/(sici)1097-4547(20000215)59:4
Self-citation
Flagged first, then by citations
2 of the 51 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Louis, 1996, Adv. Neurol., 69, 311
- Baba, 1998, Am. J. Pathol., 152, 879
- Takeda, 1998, Am. J. Pathol., 152, 367
- Lee, 2001, FASEB J., 15, 916
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The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
Oxidative Stress and Neurotoxicity
Sayre, L. M., Perry, G. L., & Smith, M. A. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700210j · Cited by 884
Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease
Zucca, F. A., Segura-Aguilar, J., Ferrari, E., Muñoz, P., Paris, I., Sulzer, D., Sarna, T., Casella, L., & Zecca, L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.09.012 · Cited by 659
Metadata
- Authors
- Norris, E. H., Giasson, B. I., Hodara, R., Xu, S., Trojanowski, J. Q., Ischiropoulos, H., & Lee, V. M.-Y.
- Affiliations
- Institute on Aging (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Lee, Virginia M.-Y.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 280
- Issue
- 22
- Pages
- 21212-21219
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1975188689
- Cited by
- 273
- References
- 51
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 9 · 2019: 21 · 2018: 14 · 2017: 8 · 2016: 5 · 2015: 17 · 2014: 17 · 2013: 15 · 2012: 13
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS044233, AG-09215)
- National Institute on Aging (AG09215, P01AG009215)
- National Institute of Neurological Disorders and Stroke (P01NS044233, NS-044233)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, fibrillization, dopamine autoxidation, conformational change, Parkinson's disease, dopaminergic neurons, substantia nigra, protein aggregation
- MeSH terms
- Circular Dichroism, Dopamine, Histidine, Humans, Methionine, Microscopy, Electron, Mutation, Nerve Tissue Proteins, Oxygen, Parkinson Disease, Peptides, Protein Conformation, Recombinant Proteins, Time Factors, Tyrosine, Mutagenesis, Protein Structure, Secondary, Spectroscopy, Fourier Transform Infrared, DNA, Complementary, Oxidative Stress, Microscopy, Atomic Force, Amino Acid Motifs, Indolequinones, Synucleins, alpha-Synuclein
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