Parkinson's disease
Abstract
Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. Clinical manifestations of this complex disease include motor impairments involving resting tremor, bradykinesia, postural instability, gait difficulty and rigidity. Current medications only provide symptomatic relief and fail to halt the death of dopaminergic neurons. A major hurdle in development of neuroprotective therapies are due to limited understanding of disease processes leading to death of dopaminergic neurons. While the etiology of dopaminergic neuronal demise is elusive, a combination of genetic susceptibilities and environmental factors seems to play a critical role. The majority of PD cases are sporadic however, the discovery of genes linked to rare familial forms of disease (encoding alpha-synuclein, parkin, DJ-1, PINK-1 and LRRK2) and studies from experimental animal models has provided crucial insights into molecular mechanisms in disease pathogenesis and identified probable targets for therapeutic intervention. Recent findings implicate mitochondrial dysfunction, oxidative damage, abnormal protein accumulation and protein phosphorylation as key molecular mechanisms compromising dopamine neuronal function and survival as the underlying cause of pathogenesis in both sporadic and familial PD. In this review we provide an overview of the most relevant findings made by the PD research community in the last year and discuss how these significant findings improved our understanding of events leading to nigrostriatal dopaminergic degeneration, and identification of potential cell survival pathways that could serve as targets for neuroprotective therapies in preventing this disabling neurological illness.
Integrity signals
Registry
Cites
Statistics
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?
Pathogenic mutations in several genes including α-synuclein, parkin, UCHL-1, DJ-1, PINK-1, LRRK-2, NURR-1, tau, and HtrA2 directly or indirectly implicate a role of mitochondrial dysfunction in familial PD pathogenesis.
“In addition to mtDNA mutations, pathogenic mutations in several genes including α–synuclein, parkin, UCHL-1, DJ-1, PINK-1, LRRK-2, NURR-1, tau, and HtrA2 also directly or indirectly implicate a role of mitochondrial dysfunction in familial PD pathogenesis3, 28, 29.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [28]
Cites
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · see citing works
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Self-citationMutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227 · see citing works
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914 · 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
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R., Sherer, T., Mackenzie, G., Garcia-Osuna, M., Panov, A., & Greenamyre, J. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,797 · see citing works
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634 · see citing works
Spillantini, 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 3,151 · see citing works
Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
Zimprich, A. A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M. J., Lincoln, S., Kachergus, J. M., Hulihan, M., Uitti, R. J., Calne, D. B., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.005 · Cited by 3,024 · see citing works
Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
Paisán‐Ruiz, C., Jain, S., Evans, E. W., Gilks, W. P., Simón, J., van der Brug, M., de Munaín, A. L., Aparicio, S. F., Gil, A. M., Khan, N. L., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.10.023 · Cited by 2,416 · see citing works
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024 · see citing works
Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788 · see citing works
Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.-M., et al. (2006) · Nature · doi:10.1038/nature04788 · Cited by 1,705 · see citing works
Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1769 · Cited by 1,570 · see citing works
Neuropathology of Parkinson's Disease
Forno, L. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199603000-00001 · Cited by 1,556 · 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
Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
West, A. B., Moore, D. J., Biskup, S., Bugayenko, A., Smith, W. W., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507360102 · Cited by 1,228 · see citing works
Canet-Aviles, R., Wilson, M. A., Miller, D. W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M. J., Ringe, D., Petsko, G. A., & Cookson, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402959101 · Cited by 1,115 · see citing works
Liberatore, G. T., Jackson-Lewis, V., Vukosavic, S., Mandir, A. S., Vila, M., McAuliffe, W. G., Dawson, V. L., Dawson, T. M., & Przedborski, S. (1999) · Nature Medicine · doi:10.1038/70978 · Cited by 1,046 · see citing works
Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice
Palacino, J. J., Sagi, D., Goldberg, M. S., Krauss, S., Motz, C., Wacker, M., Klose, J., & Shen, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401135200 · Cited by 995 · see citing works
Zhang, Y., Gao, J., Chung, K. K. K., Huang, H., Dawson, V. L., & Dawson, T. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240347797 · Cited by 982 · see citing works
Mitochondria take center stage in aging and neurodegeneration
Beal, M. F. (2005) · Annals of Neurology · doi:10.1002/ana.20624 · Cited by 957 · see citing works
Self-citationKobayashi, A., Kang, M.-I., Watai, Y., Tong, K. I., Shibata, T., Uchida, K., & Yamamoto, M. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.221-229.2006 · Cited by 933 · see citing works
Kraytsberg, Y., Kudryavtseva, E., McKee, A. C., Geula, C., Kowall, N. W., & Khrapko, K. (2006) · Nature Genetics · doi:10.1038/ng1778 · Cited by 884 · see citing works
DJ‐1 has a role in antioxidative stress to prevent cell death
Taira, T., Saito, Y., Niki, T., Iguchi‐Ariga, S. M. M., Takahashi, K., & Ariga, H. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400074 · Cited by 852 · see citing works
Expression of Nrf2 in Neurodegenerative Diseases
Ramsey, C. P., Glass, C. A., Montgomery, M. B., Lindl, K. A., Ritson, G. P., Chia, L. A., Hamilton, R. L., Chu, C. T., & Jordan-Sciutto, K. L. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e31802d6da9 · Cited by 760 · see citing works
Keeney, P., Xie, J., Capaldi, R., & Bennett, J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0984-06.2006 · Cited by 757 · see citing works
An Important Role of Nrf2-ARE Pathway in the Cellular Defense Mechanism
Lee, J., & Johnson, J. A. (2004) · BMB Reports · doi:10.5483/bmbrep.2004.37.2.139 · Cited by 746 · see citing works
Kinase activity is required for the toxic effects of mutant LRRK2/dardarin
Greggio, E., Jain, S., Kingsbury, A. E., Bandopadhyay, R., Lewis, P. A., Kaganovich, A., van der Brug, M. P., Beilina, A. G., Blackinton, J. G., Craig, K. J. T., et al. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.04.001 · Cited by 731 · see citing works
Dopamine covalently modifies and functionally inactivates parkin
LaVoie, M. J., Ostaszewski, B. L., Weihofen, A., Schlossmacher, M. G., & Selkoe, D. J. (2005) · Nature Medicine · doi:10.1038/nm1314 · Cited by 722 · see citing works
Kim, R. H., Smith, P. D., Aleyasin, H., Hayley, S. P., Mount, M. P., Pownall, S., Wakeham, A. C., You-Ten, A. J., Kalia, S. K., Horne, P., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501282102 · Cited by 697 · see citing works
The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living
Gorell, J., Johnson, C. C., Rybicki, B., Peterson, E., & Richardson, R. (1998) · Neurology · doi:10.1212/wnl.50.5.1346 · Cited by 694 · see citing works
Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration
Teismann, P., Tieu, K., Choi, D., Wu, D., Naini, A., Hunot, S., Vila, M., Jackson-Lewis, V. R., & Przedborski, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0837397100 · Cited by 659 · see citing works
Origin and functional consequences of the complex I defect in Parkinson's disease
Swerdlow, R. H., Parks, J. K., Miller, S. W., Davis, R. E., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., & Parker, W. D. (1996) · Annals of Neurology · doi:10.1002/ana.410400417 · Cited by 638 · see citing works
Kinase activity of mutant LRRK2 mediates neuronal toxicity
Smith, W. W., Pei, Z., Jiang, H., Dawson, V. L., Dawson, T. M., & Ross, C. A. (2006) · Nature Neuroscience · doi:10.1038/nn1776 · Cited by 619 · see citing works
Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons
Ekstrand, M. I., Terzioglu, M., Galter, D., Zhu, S., Hofstetter, C., Lindqvist, E., Thams, S., Bergstrand, A., Hansson, F. S., Trifunovic, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605208103 · Cited by 605 · see citing works
West, A. B., Moore, D. J., Choi, C., Andrabi, S. A., Li, X., Dikeman, D. A., Biskup, S., Zhang, Z., Lim, K., Dawson, V. L., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl471 · Cited by 592 · see citing works
Dinkova‐Kostova, A. T., Liby, K. T., Stephenson, K. K., Holtzclaw, W. D., Gao, X., Suh, N., Williams, C. R., Risingsong, R., Honda, T., Gribble, G. W., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500815102 · Cited by 575 · see citing works
The Familial Parkinsonism Gene LRRK2 Regulates Neurite Process Morphology
MacLeod, D., Dowman, J., Hammond, R., Leete, T., Inoue, K., & Abeliovich, A. (2006) · Neuron · doi:10.1016/j.neuron.2006.10.008 · Cited by 564 · see citing works
Goldberg, M. S., Pisani, A., Haburčák, M., Vortherms, T. A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.041 · Cited by 532 · see citing works
Localization of LRRK2 to membranous and vesicular structures in mammalian brain
Biskup, S., Moore, D. J., Celsi, F., Higashi, S., West, A. B., Andrabi, S. A., Kurkinen, K. M. A., Yu, S., Savitt, J. M., Waldvogel, H. J., et al. (2006) · Annals of Neurology · doi:10.1002/ana.21019 · Cited by 511 · see citing works
Oxidative Damage of DJ-1 Is Linked to Sporadic Parkinson and Alzheimer Diseases
Choi, J., Sullards, M. C., Olzmann, J. A., Rees, H. D., Weintraub, S. T., Bostwick, D. E., Gearing, M., Levey, A. I., Chin, L., & Li, L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m509079200 · Cited by 482 · see citing works
The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity
Gloeckner, C. J., Kinkl, N., Schumacher, A., Braun, R. J., O’Neill, E. E., Meitinger, T., Kölch, W., Prokisch, H., & Ueffing, M. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi439 · Cited by 477 · see citing works
Thiruchelvam, M. J., Richfield, E. K., Baggs, R. B., Tank, A. W., & Cory‐Slechta, D. A. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09207.2000 · Cited by 471 · see citing works
The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease
Bandopadhyay, R. (2004) · Brain · doi:10.1093/brain/awh054 · Cited by 466 · see citing works
Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism
Silvestri, L., Caputo, V., Bellacchio, E., Atorino, L., Dallapiccola, B., Valente, E. M., & Casari, G. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi377 · Cited by 449 · see citing works
Smith, W. W., Pei, Z., Jiang, H., Moore, D. J., Liang, Y., West, A. B., Dawson, V. L., Dawson, T. M., & Ross, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508052102 · Cited by 420 · see citing works
Zhang, L., Shimoji, M., Thomas, B., Moore, D. J., Yu, S.-W., Marupudi, N. I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi211 · Cited by 418 · see citing works
Self-citationParkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death
Darios, F. D. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg044 · Cited by 401 · see citing works
Beilina, A. G., van der Brug, M., Ahmad, R., Kesavapany, S., Miller, D. W., Petsko, G. A., & Cookson, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500617102 · Cited by 382 · see citing works
Fallon, L., Bélanger, C., Corera, A. T., Kontogiannea, M., Regan‐Klapisz, E., Moreau, F., Voortman, J., Haber, M., Rouleau, G., Thorarinsdottir, T., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1441 · Cited by 357 · see citing works
PINK1 protein in normal human brain and Parkinson's disease
Gandhi, S. (2006) · Brain · doi:10.1093/brain/awl114 · Cited by 342 · see citing works
Petit-Paitel, A., Kawarai, T., Paitel, E., Sanjo, N., Maj, M. C., Scheid, M. P., Chen, F., Gu, Y., Hasegawa, H., Salehi‐Rad, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505143200 · Cited by 329 · see citing works
Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death
Junn, E., Taniguchi, H., Jeong, B. S., Zhao, X. S., Ichijo, H., & Mouradian, M. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409635102 · Cited by 319 · see citing works
Smith, P. D., Crocker, S. J., Jackson-Lewis, V. R., Jordan‐Sciutto, K. L., Hayley, S. P., Mount, M. P., O'Hare, M. J., Callaghan, S. M., Slack, R. S., Przedborski, S., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2232515100 · Cited by 310 · see citing works
The R1441C mutation of LRRK2 disrupts GTP hydrolysis
Lewis, P. A., Greggio, E., Beilina, A. G., Jain, S., Baker, A. K., & Cookson, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.006 · Cited by 274 · see citing works
Shih, A. Y., Imbeault, S., Barakauskas, V., Erb, H., Jiang, L., Li, P., & Murphy, T. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414635200 · Cited by 273 · see citing works
Parkin enhances mitochondrial biogenesis in proliferating cells
Kuroda, Y., Mitsui, T., Kunishige, M., Shono, M., Akaike, M., Azuma, H., & Matsumoto, T. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl006 · Cited by 268 · see citing works
Ito, G., Okai, T., Fujino, G., Takeda, K., Ichijo, H., Katada, T., & Iwatsubo, T. (2007) · Biochemistry · doi:10.1021/bi061960m · Cited by 263 · see citing works
Age-dependent Motor Deficits and Dopaminergic Dysfunction in DJ-1 Null Mice
Chen, L., Cagniard, B., Mathews, T. A., Jones, S. R., Koh, H. C., Ding, Y., Carvey, P. M., Ling, Z., Kang, U. J., & Zhuang, X. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413955200 · Cited by 261 · see citing works
Bodner, R. A., Outeiro, T. F., Altmann, S. M., Maxwell, M. M., Cho, S. H., Hyman, B. T., McLean, P. J., Young, A. B., Housman, D. E., & Kazantsev, A. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511256103 · Cited by 255 · see citing works
Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress
Moore, D. J., Zhang, L., Troncoso, J. C., Lee, M. K., Hattori, N., Mizuno, Y., Dawson, T. M., & Dawson, V. L. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi007 · Cited by 245 · see citing works
α-Synuclein activates stress signaling protein kinases in THP-1 cells and microglia
Klegeris, A., Pelech, S., Giasson, B. I., Maguire, J., Zhang, H., McGeer, E. G., & McGeer, P. L. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.11.013 · Cited by 227 · see citing works
p53‐dependent neuronal cell death in a DJ‐1‐deficient zebrafish model of Parkinson's disease
Bretaud, S., Allen, C. E., Ingham, P. W., & Bandmann, O. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04291.x · Cited by 219 · see citing works
Mice lacking alpha-synuclein are resistant to mitochondrial toxins
Klivènyi, P., Siwek, D. F., Gardian, G., Yang, L., Starkov, A. A., Cléren, C., Ferrante, R. J., Kowall, N. W., Abeliovich, A., & Beal, M. F. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.018 · Cited by 213 · see citing works
Self-citationAssociation of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease
Tang, B., Xiong, H., Sun, P., Zhang, Y., Wang, D., Hu, Z., Zhu, Z.-H., Ma, H., Pan, Q., Xia, J., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl104 · Cited by 213 · see citing works
Wang, C., Ko, H. S., Thomas, B., Tsang, F., Chew, K. C. M., Tay, S.-P., Ho, M. W. L., Lim, T. M., Soong, T. W., Pletniková, O., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi413 · Cited by 206 · see citing works
Self-citationMitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6
Hoepken, H.-H., Gispert, S., Morales, B., Wingerter, O., Turco, D. D., Mülsch, A., Nussbaum, R. L., Müller, K., Dröse, S., Brandt, U., et al. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.10.007 · Cited by 202 · see citing works
LRK-1, a C. elegans PARK8-Related Kinase, Regulates Axonal-Dendritic Polarity of SV Proteins
Sakaguchi-Nakashima, A., Meir, J. Y., Jin, Y., Matsumoto, K., & Hisamoto, N. (2007) · Current Biology · doi:10.1016/j.cub.2007.01.074 · Cited by 192 · see citing works
Apoptotic mechanisms in mutant LRRK2-mediated cell death
Iaccarino, C., Crosio, C., Vitale, C., Sanna, G., Carrı̀, M. T., & Barone, P. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm080 · Cited by 190 · see citing works
In vivo modulation of the Parkinsonian phenotype by Nrf2
Burton, N. C., Kensler, T. W., & Guilarte, T. R. (2006) · NeuroToxicology · doi:10.1016/j.neuro.2006.07.019 · Cited by 187 · see citing works
Liang, C., Wang, T. T., Luby‐Phelps, K., & German, D. C. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.08.015 · Cited by 186 · see citing works
Distribution of PINK1 and LRRK2 in rat and mouse brain
Taymans, J., den Haute, C. V., & Baekelandt, V. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03919.x · Cited by 184 · see citing works
Inden, M., Taira, T., Kitamura, Y., Yanagida, T., Tsuchiya, D., Takata, K., Yanagisawa, D., Nishimura, K., Taniguchi, T., Kiso, Y., et al. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.06.004 · Cited by 180 · 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
Zhong, N., Kim, C. Y., Rizzu, P., Geula, C., Porter, D. R., Pothos, E. N., Squitieri, F., Heutink, P., & Xu, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601935200 · Cited by 178 · see citing works
Leucine-rich repeat kinase 2 associates with lipid rafts
Hatano, T., Kubo, S., Imai, S., Maeda, M., Ishikawa, K., Mizuno, Y., & Hattori, N. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm013 · Cited by 176 · see citing works
LRRK2 expression linked to dopamine‐innervated areas
Galter, D., Westerlund, M., Belin, A. C., Lindqvist, E., Sydow, O., & Olson, L. (2006) · Annals of Neurology · doi:10.1002/ana.20808 · Cited by 174 · see citing works
Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress
Muqit, M. M. K., Abou‐Sleiman, P. M., Saurin, A. T., Harvey, K., Gandhi, S., Deas, E., Eaton, S. D., Smith, M. D. P., Venner, K., Matilla‐Dueñas, A., et al. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03845.x · Cited by 172 · see citing works
Oncoprotein Akt/PKB induces trophic effects in murine models of Parkinson's disease
Ries, V., Henchcliffe, C., Kareva, T., Rzhetskaya, M., Bland, R. J., During, M. J., Kholodilov, N. G., & Burke, R. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606401103 · Cited by 168 · see citing works
Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y
Deng, H., Jankovic, J. J., Guo, Y., Xie, W., & Le, W. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.178 · Cited by 156 · see citing works
Casarejos, M. J., Menéndez, J., Solano, R. M., Rodríguez‐Navarro, J. A., de Yébenes, J. G., & Mena, M. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03777.x · Cited by 156 · see citing works
Sim, C. H., Lio, D. S. S., Mok, S. S., Masters, C. L., Hill, A. F., Culvenor, J. G., & Cheng, H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl398 · Cited by 146 · see citing works
Scheele, C. C., Petrovič, N., Faghihi, M. A., Lassmann, T., Fredriksson, K., Rooyackers, O., Wahlestedt, C., Good, L., & Timmons, J. A. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-74 · Cited by 137 · see citing works
The Role of G-Protein-Coupled Receptor Kinase 5 in Pathogenesis of Sporadic Parkinson's Disease
Arawaka, S., Wada, M., Goto, S., Karube, H., Sakamoto, M., Ren, C.-H., Koyama, S., Nagasawa, H., Kimura, H., Kawanami, T., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0341-06.2006 · Cited by 136 · see citing works
Chinta, S. J., & Andersen, J. K. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.002 · Cited by 134 · see citing works
Mutant α-synuclein exacerbates age-related decrease of neurogenesis
Winner, B., Rockenstein, E. M., Lie, D. C., Aigner, R., Mante, M., Bogdahn, U., Couillard‐Després, S., Masliah, E., & Winkler, J. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.12.016 · Cited by 125 · see citing works
Avraham, E., Rott, R., Liani, E., Szargel, R., & Engelender, S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608243200 · Cited by 121 · see citing works
Higashi, S., Moore, D. J., Colebrooke, R. E., et al. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04246.x · Cited by 116 · see citing works
Hardy, J., Cookson, M., & Singleton, A. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00350-8 · Cited by 112 · see citing works
Wong, E. S. P., Tan, J. M. M., Wang, C., Zhang, Z., Tay, S.-P., Zaiden, N., Ko, H. S., Dawson, V. L., Dawson, T. M., & Lim, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609466200 · Cited by 87 · see citing works
LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain
Simón‐Sánchez, J., Herranz‐Pérez, V., Olucha-Bordonau, F. E., & Pérez‐Tur, J. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04616.x · Cited by 87 · see citing works
Greggio, E., Lewis, P. A., van der Brug, M. P., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04523.x · Cited by 83 · see citing works
MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease
White, L. R., Toft, M., Kvam, S. N., Farrer, M. J., & Aasly, J. O. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21240 · Cited by 78 · see citing works
Parkin and defective ubiquitination in Parkinson’s disease
Dawson, T. M. (2006) · Springer eBooks · doi:10.1007/978-3-211-45295-0_32 · Cited by 74 · see citing works
Görner, K., Holtorf, E., Waak, J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609821200 · Cited by 72 · see citing works
The Drosophila parkin homologue is required for normal mitochondrial dynamics during spermiogenesis
Riparbelli, M. G., & Callaini, G. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.10.038 · Cited by 70 · see citing works
Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity
Perez, F. A., Curtis, W., & Palmiter, R. D. (2005) · BMC Neuroscience · doi:10.1186/1471-2202-6-71 · Cited by 67 · see citing works
Thomas, B., von Coelln, R., Mandir, A. S., Trinkaus, D. B., Farah, M. H., Lim, K. L., Calingasan, N. Y., Beal, M. F., Dawson, V. L., & Dawson, T. M. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.021 · Cited by 67 · see citing works
Self-citationLRRK2 protein is a component of lewy bodies
Zhu, X., Siedlak, S. L., Smith, M. A., Perry, G. L., & Chen, S. G. (2006) · Annals of Neurology · doi:10.1002/ana.20928 · Cited by 61 · see citing works
Genetic analysis of LRRK2 mutations in patients with Parkinson disease
Deng, H., Le, W., Guo, Y., Hunter, C., Xie, W., Huang, M., & Jankovic, J. J. (2006) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.09.017 · Cited by 54 · see citing works
Genetics of Parkinson’s disease and parkinsonism
Douglas, M. R., Lewthwaite, A. J., & Nicholl, D. J. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.6.657 · Cited by 52 · see citing works
Hulleman, J. D., Mirzaei, H., Guigard, E., et al. (2007) · Biochemistry · doi:10.1021/bi7001778 · Cited by 50 · see citing works
Leutenegger, A., Salih, M. A. M., Ibáñez, P., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.9.1257 · Cited by 43 · see citing works
Paterna, J., Leng, A., Weber, E., Feldon, J., & Büeler, H. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300154 · Cited by 38 · see citing works
Ting, J. P. Y., Conti, B. J., McNally, R. S., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/t2ad-zg90 · Cited by 38 · see citing works
Specific cleavage of DJ-1 under an oxidative condition
Ooe, H., Maita, C., Maita, H., Iguchi‐Ariga, S. M. M., & Ariga, H. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.06.067 · Cited by 26 · see citing works
Midbrain neuronal cultures from parkin mutant mice are resistant to nitric oxide-induced toxicity
Solano, R. M., Menéndez, J., Casarejos, M. J., Rodríguez‐Navarro, J. A., de Yébenes, J. G., & Mena, M. A. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.03.027 · Cited by 19 · see citing works
Li, C., & Beal, M. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508350102 · Cited by 17 · see citing works
Self-citationShults, C. W., Barrett, J. M., & Fontaine, D. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.07.006 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438 · see citing works
Forsyth, C. B., Shannon, K. M., Kordower, J. H., Voigt, R. M., Shaikh, M., Jaglin, J. A., Estes, J. D., Dodiya, H. B., & Keshavarzian, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028032 · Cited by 974 · see citing works
Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?
Burghes, A. H. M., & Beattie, C. E. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2670 · Cited by 723 · see citing works
Repression of α-synuclein expression and toxicity by microRNA-7
Junn, E., Lee, K.-W., Jeong, B. S., Chan, T. W., Im, J.-Y., & Mouradian, M. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906277106 · Cited by 634 · see citing works
The circadian clock and pathology of the ageing brain
Kondratova, A. A., & Kondratov, R. V. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3208 · Cited by 482 · see citing works
Mitochondrial dysfunction in ataxia-telangiectasia
Valentin-Vega, Y. A., MacLean, K. H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F. C., Cleveland, J. L., Green, D. R., & Kastan, M. B. (2012) · Blood · doi:10.1182/blood-2011-08-373639 · Cited by 365 · see citing works
Scott, L. E., & Orvig, C. (2009) · Chemical Reviews · doi:10.1021/cr9000176 · Cited by 332 · 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
Mitochondrial Approaches for Neuroprotection
Chaturvedi, R. K., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.027 · Cited by 294 · see citing works
Self-citationThe lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery
Dutta, G., Zhang, P., & Liu, B. (2008) · Fundamental & Clinical Pharmacology · doi:10.1111/j.1472-8206.2008.00616.x · Cited by 235 · see citing works
Mitochondrial Medicine for Aging and Neurodegenerative Diseases
Reddy, P. H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8044-z · Cited by 230 · see citing works
Alpha synuclein is transported into and out of the brain by the blood-brain barrier
Sui, Y.-T., Bullock, K. M., Erickson, M. A., Zhang, J., & Banks, W. A. (2014) · Peptides · doi:10.1016/j.peptides.2014.09.018 · Cited by 212 · see citing works
The role of free radicals in the aging brain and Parkinson’s Disease: Convergence and parallelism
Kumar, H., Lim, H.-W., More, S. V., Kim, B.-W., Koppula, S., Kim, I. S., & Choi, D.-K. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130810478 · Cited by 212 · see citing works
Zhou, Z.-L., Jia, X.-B., Sun, M.-F., Zhu, Y.-L., Qiao, C.-M., Zhang, B.-P., Zhao, L.-P., Yang, Q., Cui, C., Chen, X., et al. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00719-2 · Cited by 195 · see citing works
Synthesis and transport of creatine in the CNS: Importance for cerebral functions
Béard, E., & Braissant, O. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06935.x · Cited by 192 · see citing works
Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson's disease
Moreira, S., Fonseca, I., Nunes, M. J., Rosa, A., Lemos, L., Rodrigues, E., Carvalho, A. N., Outeiro, T. F., Rodrigues, C. M. P., Gama, M. J., et al. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.05.009 · Cited by 112 · see citing works
Tauroursodeoxycholic acid improves motor symptoms in a mouse model of Parkinson's disease
Rosa, A. I., Duarte-Silva, S., Silva-Fernandes, A., Nunes, M. J., Carvalho, A. N., Rodrigues, E., Gama, M. J., Rodrigues, C. M. P., Maciel, P., & Castro-Caldas, M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1062-4 · Cited by 94 · see citing works
Morris, G., Anderson, G., Berk, M., & Maes, M. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8477-8 · Cited by 96 · see citing works
A review of creatine supplementation in age-related diseases: more than a supplement for athletes
Smith, R. N., Agharkar, A. S., & Gonzales, E. B. (2014) · F1000Research · doi:10.12688/f1000research.5218.1 · Cited by 82 · see citing works
Rosa, A. I., Fonseca, I., Nunes, M. J., Moreira, S., Rodrigues, E., Carvalho, A. N., Rodrigues, C. M. P., Gama, M. J., & Castro-Caldas, M. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.06.004 · Cited by 82 · see citing works
Loss of <i>Parkin</i> impairs mitochondrial function and leads to muscle atrophy
Peker, N., Donipadi, V., Sharma, M., McFarlane, C., & Kambadur, R. (2018) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00064.2017 · Cited by 68 · see citing works
Mendes, M. O., Rosa, A. I., Carvalho, A. N., Nunes, M. J., Dionísio, P., Rodrigues, E., Costa, D., Duarte-Silva, S., Maciel, P., Rodrigues, C. M. P., et al. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.01.003 · Cited by 31 · see citing works
- Authors
- Thomas, B., & Beal, M. F.
- Affiliations
- Cornell University (US)
- Corresponding author
- Thomas, B.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-07-31
- Volume
- 16
- Issue
- R2
- Pages
- R183-R194
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W4246230178
- Cited by
- 748
- References
- 111
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 31 · 2023: 21 · 2022: 20 · 2021: 27 · 2020: 29 · 2019: 42 · 2018: 49 · 2017: 46 · 2016: 35 · 2015: 39 · 2014: 45 · 2013: 50 · 2012: 35
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- 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 › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, nigrostriatal dopaminergic neurons, neurodegeneration, neuroprotective therapy, mitochondrial dysfunction, oxidative stress, alpha-synuclein, Parkin, DJ-1, PINK1, LRRK2, familial Parkinson's disease, sporadic Parkinson's disease, protein aggregation, protein phosphorylation, cell survival pathways, pathogenesis
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Protein Deglycase DJ-1, PTEN-Induced Putative Kinase, Humans, Mitochondria, Models, Biological, Mutation, Oxidation-Reduction, Parkinson Disease, Protein Kinases, Oncogene Proteins, Protein Serine-Threonine Kinases, Genetic Predisposition to Disease, Ubiquitin-Protein Ligases, Intracellular Signaling Peptides and Proteins, alpha-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
