α-Synuclein Overexpression Increases Cytosolic Catecholamine Concentration
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Dysregulation of dopamine homeostasis and elevation of the cytosolic level of the transmitter have been suggested to underlie the vulnerability of catecholaminergic neurons in Parkinson's disease. Because several known mutations in alpha-synuclein or overexpression of the wild-type (WT) protein causes familial forms of Parkinson's disease, we investigated possible links between alpha-synuclein pathogenesis and dopamine homeostasis. Chromaffin cells isolated from transgenic mice that overexpress A30P alpha-synuclein displayed significantly increased cytosolic catecholamine levels as measured by intracellular patch electrochemistry, whereas cells overexpressing the WT protein and those from knock-out animals were not different from controls. Likewise, catechol concentrations were higher in L-DOPA-treated PC12 cells overexpressing A30P or A53T compared with those expressing WT alpha-synuclein, although the ability of cells to maintain a low cytosolic dopamine level after L-DOPA challenge was markedly inhibited by either protein. We also found that incubation with low-micromolar concentrations of WT, A30P, or A53T alpha-synuclein inhibited ATP-dependent maintenance of pH gradients in isolated chromaffin vesicles and that the WT protein was significantly less potent in inducing the proton leakage. In summary, we demonstrate that overexpression of different types of alpha-synuclein disrupts vesicular pH and leads to a marked increase in the levels of cytosolic catechol species, an effect that may in turn trigger cellular oxyradical damage. Although multiple molecular mechanisms may be responsible for the perturbation of cytosolic catecholamine homeostasis, this study provides critical evidence about how alpha-synuclein might exert its cytotoxicity and selectively damage catecholaminergic cells.
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High cytosolic concentrations of free DA can produce oxidative stress and interact with α-syn, promoting neurodegeneration.
“The high cytosolic concentrations of free DA can produce oxidative stress and can interact with α-syn, promoting the neurodegenerative process (Mosharov et al., 2006).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Mosharov et al., 2006
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Greene, L., & Tischler, A. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.7.2424 · Cited by 5,594 · see citing works
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469 · see citing works
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D. (2004) · Science · doi:10.1126/science.1101738 · Cited by 2,024 · cited 4× · see citing works
“, 2005) or an inhibition of protein degradation via chaperone-mediated autophagy (Cuervo et al., 2004) or the proteosome pathway (Stefanis et al.”
BackgroundInfluentialStabilization 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
Conway, 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 1,543 · see citing works
Conway, K. A., Harper, J. D., & Lansbury, P. T. (1998) · Nature Medicine · doi:10.1038/3311 · Cited by 1,501 · see citing works
MOLECULAR PATHOPHYSIOLOGY OF PARKINSON'S DISEASE
Moore, D. J., West, A. B., Dawson, V. L., & Dawson, T. M. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135718 · Cited by 1,274 · see citing works
Eliezer, D., Kutluay, E., Bussell, R., & Browne, G. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4538 · Cited by 1,077 · see citing works
Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein
Giasson, B. I., Forman, M. S., Higuchi, M., Golbe, L. I., Graves, C. L., Kotzbauer, P. T., Trojanowski, J. Q., & Lee, V. M.-Y. (2003) · Science · doi:10.1126/science.1082324 · Cited by 879 · cited 1× · see citing works
“Monomeric -synuclein is mainly unfolded in solution (Eliezer et al., 2001); however, both WT and mutant -synuclein can form oligomeric protofibrils and amyloid fibrils that resemble those in Lewy bodies (Conway et al., 1998; Giasson et al., 2003).”
BackgroundYeast Cells Provide Insight into Alpha-Synuclein Biology and Pathobiology
Outeiro, T. F., & Lindquist, S. L. (2003) · Science · doi:10.1126/science.1090439 · Cited by 808 · see citing works
Lashuel, H. A., Petre, B. M., Wall, J. S., Simon, M. N., Nowak, R. J., Walz, T., & Lansbury, P. T. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00735-0 · Cited by 802 · see citing works
Conway, K. A., Harper, J. D., & Lansbury, P. T. (2000) · Biochemistry · doi:10.1021/bi991447r · Cited by 786 · see citing works
Volles, M. J., Lee, S., Rochet, J., Shtilerman, M. D., Ding, T. T., Kessler, J. C., & Lansbury, P. T. (2001) · Biochemistry · doi:10.1021/bi0102398 · Cited by 682 · see citing works
A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter
Liu, Y. (1992) · Cell · doi:10.1016/0092-8674(92)90425-c · Cited by 589 · see citing works
Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP
Dauer, W. T., Kholodilov, N. G., Vila, M., Trillat, A., Goodchild, R. E., Larsen, K. E., Staal, R. G. W., Tieu, K., Schmitz, Y., Yuan, C. A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172514599 · Cited by 580 · see citing works
Stefanis, L., Larsen, K. E., Rideout, H. J., Sulzer, D. L., & Greene, L. A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09549.2001 · Cited by 569 · see citing works
The exocytotic event in chromaffin cells revealed by patch amperometry
Albillos, A., Dernick, G., Horstmann, H., Almers, W., de Toledo, G. Á., & Lindau, M. (1997) · Nature · doi:10.1038/39081 · Cited by 568 · see citing works
Parkin Protects against the Toxicity Associated with Mutant α-Synuclein
Petrucelli, L., O’Farrell, C., Lockhart, P. J., Baptista, M. J., Kehoe, K. J., Vink, L., Choi, P., Wolozin, B. L., Farrer, M. J., Hardy, J., et al. (2002) · Neuron · doi:10.1016/s0896-6273(02)01125-x · Cited by 552 · see citing works
Lipid Rafts Mediate the Synaptic Localization of α-Synuclein
Fortin, D. L., Troyer, M. D., Nakamura, K., Kubo, S., Anthony, M. D., & Edwards, R. H. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1594-04.2004 · Cited by 518 · see citing works
Binding of α-Synuclein to Brain Vesicles Is Abolished by Familial Parkinson's Disease Mutation
Jensen, P. H., Nielsen, M. S., Jakes, R., Dotti, C. G., & Goedert, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.41.26292 · Cited by 512 · see citing works
Tanaka, Y. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.9.919 · Cited by 497 · see citing works
LaVoie, M. J., & Hastings, T. G. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-04-01484.1999 · Cited by 449 · see citing works
Cubells, J. F., Rayport, S., Rajendran, G., & Sulzer, D. L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-02260.1994 · Cited by 448 · see citing works
Sulzer, D., & Rayport, S. (1990) · Neuron · doi:10.1016/0896-6273(90)90339-h · Cited by 389 · see citing works
Effect of Mutant α-Synuclein on Dopamine Homeostasis in a New Human Mesencephalic Cell Line
Lotharius, J., Barg, S., Wiekop, P., Lundberg, C., Raymon, H. K., & Brundin, P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205518200 · Cited by 349 · see citing works
Rukenstein, A., Rydel, R. E., & Greene, L. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-08-02552.1991 · Cited by 337 · see citing works
Larsen, K. E., Fon, E. A., Hastings, T. G., Edwards, R. H., & Sulzer, D. L. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08951.2002 · Cited by 335 · see citing works
Johnson, R. G. (1988) · Physiological Reviews · doi:10.1152/physrev.1988.68.1.232 · Cited by 323 · see citing works
The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation
Lotharius, J., & O’Malley, K. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005385200 · Cited by 306 · see citing works
Fast-scan voltammetry of biogenic amines
Baur, J. E., Kristensen, E. W., May, L. J., Wiedemann, D. J., & Wightman, R. M. (1988) · Analytical Chemistry · doi:10.1021/ac00164a006 · Cited by 301 · see citing works
Song, D. D., Shults, C. W., Sisk, A., Rockenstein, E. M., & Masliah, E. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00342-x · Cited by 294 · see citing works
Gosavi, N., Lee, H.-J., Lee, J. S., Patel, S. S., & Lee, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208194200 · Cited by 294 · see citing works
Intraneuronal dopamine-quinone synthesis: a review
Sulzer, D., & Zecca, L. (1999) · Neurotoxicity Research · doi:10.1007/bf03033289 · Cited by 284 · see citing works
Genetic clues to the pathogenesis of Parkinson's disease
Vila, M., & Przedborski, S. (2004) · Nature Medicine · doi:10.1038/nm1068 · Cited by 254 · see citing works
ANALYSIS OF THE MG++-ATP DEPENDENT STORAGE MECHANISM IN THE AMINE GRANULES OF THE ADRENAL MEDULLA.
Carlsson, A., Hillarp, N. ‐., & Waldeck, B. (1963) · PubMed · Cited by 232 · see citing works
Jo, E., Fuller, N., Rand, R. P., George‐Hyslop, P. S., & Fraser, P. E. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5269 · Cited by 231 · see citing works
A Combinatorial Code for the Interaction of α-Synuclein with Membranes
Kubo, S., Nemani, V. M., Chalkley, R. J., Anthony, M. D., Hattori, N., Mizuno, Y., Edwards, R. H., & Fortin, D. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504894200 · Cited by 197 · see citing works
Rochet, J., Outeiro, T. F., Conway, K. A., Ding, T. T., Volles, M. J., Lashuel, H. A., Bieganski, R. M., Lindquist, S. L., & Lansbury, P. T. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:1-2:023 · Cited by 191 · see citing works
Sidhu, A., Wersinger, C., & Vernier, P. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.03.063 · Cited by 170 · see citing works
Intracellular Patch Electrochemistry: Regulation of Cytosolic Catecholamines in Chromaffin Cells
Mosharov, E. V., Gong, L., Khanna, B., Sulzer, D. L., & Lindau, M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05835.2003 · Cited by 145 · see citing works
Chien, J. B., Wallingford, R. A., & Ewing, A. G. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb01918.x · Cited by 137 · see citing works
Could a loss of α‐synuclein function put dopaminergic neurons at risk?
Perez, R. G., & Hastings, T. G. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02423.x · Cited by 133 · see citing works
l ‐3,4‐Dihydroxyphenylalanine Increases the Quantal Size of Exocytotic Dopamine Release In Vitro
Pothos, E. N., Desmond, M., & Sulzer, D. L. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66020629.x · Cited by 130 · see citing works
Jicha, G. A., Berenfeld, B., & Davies, P. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990315)55:6 · Cited by 123 · see citing works
Parkinson disease: etiology, pathogenesis and future of gene therapy
Shastry, B. S. (2001) · Neuroscience Research · doi:10.1016/s0168-0102(01)00254-1 · Cited by 115 · see citing works
Gene dosage and pathogenesis of Parkinson's disease
Eriksen, J. L., Przedborski, S., & Petrucelli, L. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.01.001 · Cited by 108 · see citing works
[48] Chromaffin granule proton pump
Nelson, N., Cidon, S., & Moriyama, Y. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)57110-0 · Cited by 27 · see citing works
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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 · see citing works
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446 · see citing works
Dopamine-modified α-synuclein blocks chaperone-mediated autophagy
Martínez‐Vicente, M., Tallóczy, Z., Kaushik, S., Massey, A. C., Mazzulli, J. R., Mosharov, E. V., Hodara, R., Fredenburg, R. A., Wu, D.-C., Follenzi, A., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32806 · Cited by 633 · 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
Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease
Sulzer, D. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.009 · Cited by 583 · see citing works
Mosharov, E. V., Larsen, K. E., Kanter, E., Phillips, K. A., Wilson, K., Schmitz, Y., Krantz, D. E., Kobayashi, K., Edwards, R. H., & Sulzer, D. L. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.033 · Cited by 530 · see citing works
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
α-Synuclein and neuronal cell death
Cookson, M. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-9 · Cited by 420 · see citing works
Larsen, K. E., Schmitz, Y., Troyer, M. D., Mosharov, E. V., Dietrich, P., Quazi, A. Z., Savalle, M., Nemani, V. M., Chaudhry, F. A., Edwards, R. H., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3821-06.2006 · Cited by 415 · see citing works
The PC12 cell as model for neurosecretion
Westerink, R. H. S., & Ewing, A. G. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01805.x · Cited by 408 · see citing works
Deas, E., Cremades, N., Angelova, P. R., Ludtmann, M. H. R., Yao, Z., Chen, S. W., Horrocks, M. H., Banushi, B., Little, D., Devine, M. J., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6343 · Cited by 360 · see citing works
Pathological roles of α-synuclein in neurological disorders
Vekrellis, K., Xilouri, M., Emmanouilidou, E., Rideout, H. J., & Stefanis, L. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70213-7 · Cited by 359 · see citing works
Xilouri, M., Vogiatzi, T., Vekrellis, K., Park, D. S., & Stefanis, L. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005515 · Cited by 353 · see citing works
Oxidative and nitrosative stress in Parkinson's disease
Tsang, A. H. K., & Chung, K. K. K. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.12.006 · Cited by 300 · see citing works
Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps
Levy, O. A., Malagelada, C., & Greene, L. A. (2009) · APOPTOSIS · doi:10.1007/s10495-008-0309-3 · Cited by 287 · see citing works
Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model
Hamamichi, S., Rivas, R. N., Knight, A. L., Cao, S., Caldwell, K. A., & Caldwell, G. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711018105 · Cited by 285 · see citing works
Monzani, E., Nicolis, S., Dell’Acqua, S., Capucciati, A., Bacchella, C., Zucca, F. A., Mosharov, E. V., Sulzer, D. L., Zecca, L., & Casella, L. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201811122 · Cited by 270 · see citing works
Impaired dopamine release in Parkinson’s disease
Cramb, K. M. L., Beccano-Kelly, D., Cragg, S. J., & Wade-Martins, R. (2023) · Brain · doi:10.1093/brain/awad064 · Cited by 207 · see citing works
Chung, S. Y., Kishinevsky, S., Mazzulli, J. R., Graziotto, J. J., Mrejeru, A., Mosharov, E. V., Puspita, L., Valiulahi, P., Sulzer, D. L., Milner, T. A., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.08.012 · Cited by 201 · see citing works
Lam, H. A., Wu, N., Cely, I., Kelly, R. L., Hean, S., Richter, F., Magen, I., Cepeda, C., Ackerson, L. C., Walwyn, W., et al. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22611 · Cited by 184 · see citing works
Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage
Stichel, C. C., Zhu, X., Bader, V., Linnartz‐Gerlach, B., Schmidt, S., & Lübbert, H. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm083 · Cited by 179 · see citing works
Cell systems and the toxic mechanism(s) of α-synuclein
Cookson, M., & van der Brug, M. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.05.022 · Cited by 173 · see citing works
Grammatopoulos, T. N., Jones, S. M., Ahmadi, F. A., Hoover, B. R., Snell, L. D., Skoch, J. M., Jhaveri, V. V., Poczobutt, A. M., Weyhenmeyer, J. A., & Zawada, W. M. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-1 · Cited by 165 · see citing works
Perfeito, R., Cunha‐Oliveira, T., & Rego, A. C. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.042 · Cited by 165 · see citing works
Goldstein, D. S., Kopin, I. J., & Sharabi, Y. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.06.006 · Cited by 168 · see citing works
Gaugler, M. N. M., Genç, Ö., Bobela, W., Mohanna, S., Ardah, M. T., El‐Agnaf, O. M. A., Cantoni, M., Bensadoun, J., Schneggenburger, R., Knott, G. W., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0963-y · Cited by 150 · see citing works
Tan, S. H., Karri, V., Tay, N. W. R., Chang, K. H., Ah, H. Y., Ng, P. Q., Ho, H. S., Keh, H. W., & Candasamy, M. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.12.101 · Cited by 148 · see citing works
Dysautonomia in Parkinson Disease
Goldstein, D. S. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130026 · Cited by 140 · see citing works
Cartier, E. A., Parra‐Rivas, L. A., Baust, T. B., Quiroz, M. E., Salazar, G., Faúndez, V., Egaña, L. A., & Torres, G. E. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.054510 · Cited by 139 · see citing works
Kurz, A., Double, K. L., Lastres‐Becker, I., Tozzi, A., Tantucci, M., Bockhart, V., von Bonin, M., Garcı́a-Arencibia, M., Nuber, S., Schlaudraff, F., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011464 · Cited by 134 · see citing works
Deurwaerdère, P. D., Giovanni, G. D., & Millan, M. J. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.07.002 · Cited by 123 · see citing works
Physiological and pathological properties of α-synuclein
Tofaris, G. K., & Spillantini, M. G. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7217-5 · Cited by 117 · see citing works
Altered vesicular dopamine storage in Parkinson's disease: a premature demise
Caudle, W. M., Colebrooke, R. E., Emson, P. C., & Miller, G. W. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.010 · Cited by 119 · see citing works
Chapter 6 Molecular and Cellular Biology of Synucleins
Surguchov, A. P. (2008) · International review of cytology · doi:10.1016/s1937-6448(08)01406-8 · Cited by 118 · see citing works
Taylor, T. N., Caudle, W. M., & Miller, G. W. (2011) · Parkinson s Disease · doi:10.4061/2011/124165 · Cited by 113 · see citing works
Zhao, X., Kong, D., Zhou, Q., Wei, G., Song, J., Liang, Y., & Du, G. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111556 · Cited by 108 · see citing works
Botella, J., Bayersdorfer, F., & Schneuwly, S. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.11.013 · Cited by 107 · see citing works
Perfeito, R., Cunha‐Oliveira, T., & Rego, A. C. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.08.569 · Cited by 108 · see citing works
Lieberman, O. J., McGuirt, A. F., Mosharov, E. V., Pigulevskiy, I., Hobson, B. D., Choi, S., Frier, M. D., Santini, E., Borgkvist, A., & Sulzer, D. L. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.044 · Cited by 104 · see citing works
Functional and Pathological Effects of α-Synuclein on Synaptic SNARE Complexes
Gao, V., Briano, J. A., Komer, L. E., & Burré, J. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167714 · Cited by 96 · see citing works
Wise, R. M., Wagener, A., Fietzek, U. M., Klopstock, T., Mosharov, E. V., Zucca, F. A., Sulzer, D. L., Zecca, L., & Burbulla, L. F. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105920 · Cited by 95 · see citing works
Synaptic vesicle trafficking and Parkinson's disease
Esposito, G., Clara, F. A., & Verstreken, P. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20916 · Cited by 95 · see citing works
Modelling Parkinson’s Disease in Drosophila
Botella, J., Bayersdorfer, F., Gmeiner, F., & Schneuwly, S. (2009) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8098-6 · Cited by 92 · see citing works
Vergo, S. B., Johansen, J. L., Leist, M., & Lotharius, J. (2007) · Brain Research · doi:10.1016/j.brainres.2007.09.028 · Cited by 89 · see citing works
Tyrosine hydroxylase phosphorylation in vivo
Dunkley, P. R., & Dickson, P. W. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14675 · Cited by 85 · see citing works
Alpha-synuclein modulates dopamine neurotransmission
Butler, B., Sambo, D. O., & Khoshbouei, H. (2016) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2016.06.001 · Cited by 71 · see citing works
Nonaggregated α-Synuclein Influences SNARE-Dependent Vesicle Docking via Membrane Binding
Lai, Y., Kim, S., Varkey, J., Lou, X., Song, J., Diao, J., Langen, R., & Shin, Y. (2014) · Biochemistry · doi:10.1021/bi5002536 · Cited by 84 · see citing works
Post, M. R., Lieberman, O. J., & Mosharov, E. V. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00161 · Cited by 79 · see citing works
DT-Diaphorase Prevents Aminochrome-Induced Alpha-Synuclein Oligomer Formation and Neurotoxicity
Muñoz, P., Cárdenas, S., Huenchuguala, S., Briceño, A., Couve, E., Paris, I. B., & Segura‐Aguilar, J. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv016 · Cited by 79 · see citing works
Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases
Goldstein, D. S., Holmes, C. S., Kopin, I. J., & Sharabi, Y. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45803 · Cited by 78 · see citing works
Presynaptic effects of levodopa and their possible role in dyskinesia
Mosharov, E. V., Borgkvist, A., & Sulzer, D. L. (2014) · Movement Disorders · doi:10.1002/mds.26103 · Cited by 77 · see citing works
Targeting the Progression of Parkinsons Disease
George, J., Mok, S., Moses, D., Wilkins, S., Bush, A., Cherny, R., & Finkelstein, D. (2009) · Current Neuropharmacology · doi:10.2174/157015909787602814 · Cited by 77 · see citing works
Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite
Bruning, J. M., Wang, Y., Oltrabella, F., Tian, B., Kholodar, S. A., Liu, H., Bhattacharya, P., Guo, S., Holton, J. M., Fletterick, R. J., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.02.002 · Cited by 78 · see citing works
Mechanisms of alpha-synuclein toxicity: An update and outlook
Brás, I. C., Xylaki, M., & Outeiro, T. F. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.005 · Cited by 73 · see citing works
Lawal, H. O., Chang, H.-Y., Terrell, A. N., Brooks, E. S., Pulido, D., Simon, A. F., & Krantz, D. E. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.008 · Cited by 72 · see citing works
Clues to how alpha‐synuclein damages neurons in Parkinson's disease
Sulzer, D. L. (2010) · Movement Disorders · doi:10.1002/mds.22639 · Cited by 68 · see citing works
Effects of UCH‐L1 on α‐synuclein over‐expression mouse model of Parkinson’s disease
Yasuda, T., Nihira, T., Ren, Y., Cao, X., Wada, K., Setsuie, R., Kabuta, T., Wada, K., Hattori, N., Mizuno, Y., et al. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05827.x · Cited by 67 · see citing works
The heart of PD: Lewy body diseases as neurocardiologic disorders
Goldstein, D. S., & Sharabi, Y. (2017) · Brain Research · doi:10.1016/j.brainres.2017.09.033 · Cited by 67 · see citing works
Lohr, K. M., Stout, K. A., Dunn, A. R., Wang, M., Salahpour, A., Guillot, T. S., & Miller, G. W. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00010 · Cited by 67 · see citing works
Cebrián, C., Loike, J. D., & Sulzer, D. (2014) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2014_356 · Cited by 65 · see citing works
Xie, W., Wan, O. W., & Chung, K. K. K. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.014 · Cited by 64 · see citing works
Differential responses of components of the autonomic nervous system
Goldstein, D. S. (2013) · Handbook of clinical neurology · doi:10.1016/b978-0-444-53491-0.00002-x · Cited by 59 · see citing works
α-Synuclein overexpression increases dopamine toxicity in BE(2)-M17 cells
Bisaglia, M., Greggio, E., Maric, D., Miller, D. W., Cookson, M., & Bubacco, L. (2010) · BMC Neuroscience · doi:10.1186/1471-2202-11-41 · Cited by 55 · see citing works
Type-2 alkenes mediate synaptotoxicity in neurodegenerative diseases
LoPachin, R. M., Gavin, T., & Barber, D. S. (2008) · NeuroToxicology · doi:10.1016/j.neuro.2008.04.016 · Cited by 52 · see citing works
Interaction between Neuromelanin and Alpha-Synuclein in Parkinson’s Disease
Xu, S., & Chan, P. (2015) · Biomolecules · doi:10.3390/biom5021122 · Cited by 51 · see citing works
Disruption of dopamine homeostasis underlies selective neurodegeneration mediated by α‐synuclein
Park, S. S., Schulz, E. M., & Lee, D. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05929.x · Cited by 50 · see citing works
Janitzky, K. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00371 · Cited by 50 · see citing works
Bellucci, A., Navarria, L., Zaltieri, M., Missale, C., & Spano, P. (2011) · Brain Research · doi:10.1016/j.brainres.2011.11.031 · Cited by 48 · see citing works
Parkinson's disease: 10 years of progress, 1997–2007
Fahn, S. (2010) · Movement Disorders · doi:10.1002/mds.22796 · Cited by 48 · see citing works
α-Synuclein aggregation modulation: an emerging approach for the treatment of Parkinson's disease.
Singh, S., Dutta, A. K., & Modi, G. (2017) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0016 · Cited by 43 · see citing works
Qi, L., Thomas, E., White, S. H., Smith, S. K., Lee, C. A., Wilson, L. R., & Sombers, L. A. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b01871 · Cited by 47 · see citing works
Willems, S., & Merk, D. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00585 · Cited by 46 · see citing works
Tyrosine hydroxylase activity is regulated by two distinct dopamine‐binding sites
Gordon, S. L., Quinsey, N. S., Dunkley, P. R., & Dickson, P. W. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05509.x · Cited by 45 · see citing works
Goldstein, D. S., Jinsmaa, Y., Sullivan, P., Holmes, C. S., Kopin, I. J., & Sharabi, Y. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.230201 · Cited by 44 · see citing works
Relevance of chronic stress and the two faces of microglia in Parkinson's disease
Herrera, A. J., Espinosa-Oliva, A. M., Carrillo-Jiménez, A., Oliva-Martín, M. J., García-Revilla, J., García-Quintanilla, A., de Pablos, R. M., & Venero, J. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00312 · Cited by 42 · see citing works
Goldstein, D. S., & Kopin, I. J. (2017) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0497-x · Cited by 40 · see citing works
Cao, P., Yuan, Y., Pehek, E. A., Moise, A. R., Huang, Y., Palczewski, K., & Feng, Z. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009312 · Cited by 40 · see citing works
Biophysical groundwork as a hinge to unravel the biology of α-synuclein aggregation and toxicity
Plotegher, N., Greggio, E., Bisaglia, M., & Bubacco, L. (2014) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583513000097 · Cited by 39 · see citing works
Carmichael, K., Sullivan, B. T., Lopez, E., Sun, L., & Cai, H. (2021) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2021.07 · Cited by 46 · see citing works
Ong, L. K., Guan, L., Damanhuri, H. A., Goodchild, A. K., Bobrovskaya, L., Dickson, P. W., & Dunkley, P. R. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12482 · Cited by 36 · see citing works
Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases
Goldstein, D. S. (2012) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-011-9780-4 · Cited by 34 · see citing works
Alpha‐synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats
Boyer, F., & Dreyer, J. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05878.x · Cited by 34 · see citing works
? - synuclein and Parkinson's disease: the first roadblock
Chua, C. E. L., & Tang, B. L. (2006) · Journal of Cellular and Molecular Medicine · doi:10.2755/jcmm010.004.04 · Cited by 34 · see citing works
Goldstein, D. S., Sullivan, P., Holmes, C. S., Miller, G. W., Sharabi, Y., & Kopin, I. J. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12766 · Cited by 33 · see citing works
The possible involvement of mitochondrial dysfunctions in Lewy body dementia: a systematic review
Spano, M. (2015) · Functional Neurology · doi:10.11138/fneur/2015.30.3.151 · Cited by 36 · see citing works
Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson’s Disease
Ahuja, M., Kaidery, N. A., Dutta, D., Attucks, O. C., Kazakov, E. H., Gazaryan, I. G., Matsumoto, M., Igarashi, K., Sharma, S. M., & Thomas, B. (2022) · Antioxidants · doi:10.3390/antiox11091780 · Cited by 34 · see citing works
Apoptosis signal-regulating kinase 1 modulates the phenotype of α-synuclein transgenic mice
Lee, K. W., Woo, J.-M., Im, J. Y., Park, E. S., He, L., Ichijo, H., Junn, E., & Mouradian, M. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.034 · Cited by 32 · see citing works
α-synuclein and Parkinson’s disease: a proteomic view
Fasano, M., & Lopiano, L. (2008) · Expert Review of Proteomics · doi:10.1586/14789450.5.2.239 · Cited by 31 · see citing works
Dopamine Selectively Sensitizes Dopaminergic Neurons to Rotenone-Induced Apoptosis
Ahmadi, F. A., Grammatopoulos, T. N., Poczobutt, A. M., Jones, S. M., Snell, L. D., Das, M., & Zawada, W. M. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9532-5 · Cited by 29 · see citing works
Zhu, W., Tao, M., Hong, Y., Wu, S., Chu, C., Zheng, Z., Han, X., Zhu, Q., Xu, M., Ewing, A. G., et al. (2022) · Chemical Science · doi:10.1039/d2sc00809b · Cited by 28 · see citing works
de Oliveira, M. R., da Rocha, R. F., Pasquali, M. A. D. B., & Moreira, J. C. F. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2012.01.005 · Cited by 28 · see citing works
PC12 Cells as a model for parkinson's disease research
Malagelada, C., & Greene, L. A. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374028-1.00029-4 · Cited by 27 · see citing works
α - synuclein and Parkinson's disease: the first roadblock
Chua, C. E. L., & Tang, B. L. (2006) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2006.tb00528.x · Cited by 27 · see citing works
Ninkina, N. N., Millership, S. J., Peters, O. M., Connor‐Robson, N., Chaprov, K., Kopylov, A. T., Montoya, A., Kramer, H., Withers, D. J., & Buchman, V. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101375 · Cited by 25 · see citing works
Loavenbruck, A. J., & Sandroni, P. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1087988 · Cited by 24 · see citing works
Stress, allostatic load, catecholamines, and other neurotransmitters in neurodegenerative diseases
Goldstein, D. S. (2011) · Endocrine Regulations · doi:10.4149/endo_2011_02_91 · Cited by 24 · see citing works
Cell Models for the Study of Sex Steroid Hormone Neurobiology
Su, C., Rybalchenko, N., & Schreihofer, D. A. (2012) · Journal of Steroids & Hormonal Science · doi:10.4172/2157-7536.s2-003 · Cited by 23 · see citing works
Llorente‐Folch, I., Sahún, I., Contreras, L., Casarejos, M. J., Grau, J. M., Saheki, T., Mena, M. A., Satrústegui, J., Dierssen, M., & Pardo, B. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12096 · Cited by 23 · see citing works
The role of gamma‐synuclein in cocaine‐induced behaviour in rats
Boyer, F., & Dreyer, J. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06198.x · Cited by 22 · see citing works
Prasad, K., Tarasewicz, E., Ohman‐Strickland, P., O’Neill, M. J., Mitchell, S. N., Merchant, K., Tep, S., Hilton, K., Datwani, A., Buttini, M., et al. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07558.x · Cited by 21 · see citing works
- Authors
- Mosharov, E. V., Staal, R. G. W., Bové, J., Prou, D., Hananiya, A., Markov, D., Poulsen, N., Larsen, K. E., Moore, C. M. H., Troyer, M. D., Edwards, R. H., Przedborski, S., & Sulzer, D.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-09-06
- Volume
- 26
- Issue
- 36
- Pages
- 9304-9311
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674515
- OpenAlex
- W2160818993
- Cited by
- 165
- References
- 47
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 9 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 11 · 2014: 12 · 2013: 9 · 2012: 7
- FWCI
- 10.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Parkinson Foundation
- Muscular Dystrophy Association
- National Institutes of Health
- Parkinsonfonden
- National Institute on Aging (AG021191, R01AG021191)
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, Parkinson's disease, dopamine homeostasis, catecholaminergic neurons, A53T alpha-synuclein, chromaffin cells, PC12 cells, proton leak, L-DOPA, oxidative stress, alpha-synuclein overexpression
- MeSH terms
- Animals, Catecholamines, Cells, Cultured, Cytosol, Gene Expression Regulation, Mice, Transgenic, PC12 Cells, Chromaffin Cells, Mice, Rats, alpha-Synuclein
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