The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson’s disease
Open accessAbstract
c-Abl is activated in the brain of Parkinson's disease (PD) patients and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice where it inhibits parkin through tyrosine phosphorylation leading to the accumulation of parkin substrates, and neuronal cell death. In the present study, we evaluated the in vivo efficacy of nilotinib, a brain penetrant c-Abl inhibitor, in the acute MPTP-induced model of PD. Our results show that administration of nilotinib reduces c-Abl activation and the levels of the parkin substrate, PARIS, resulting in prevention of dopamine (DA) neuron loss and behavioral deficits following MPTP intoxication. On the other hand, we observe no reduction in the tyrosine phosphorylation of parkin and the parkin substrate, AIMP2 suggesting that the protective effect of nilotinib may, in part, be parkin-independent or to the pharmacodynamics properties of nilotinib. This study provides a strong rationale for testing other brain permeable c-Abl inhibitors as potential therapeutic agents for the treatment of PD.
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
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.
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?
Nilotinib succeeds in preventing DA neuron degeneration in Tg2576 mice, similarly to what observed in PD animals.
“These data prove that, similarly to what observed in PD animals (Hebron et al., 2013a; Karuppagounder et al., 2014), Nilotinib succeeds in preventing DA neuron degeneration also in Tg2576 mice.”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Karuppagounder et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563 · see citing works
Molecular Pathways of Neurodegeneration in Parkinson's Disease
Dawson, T. M., & Dawson, V. L. (2003) · Science · doi:10.1126/science.1087753 · Cited by 1,659 · see citing works
PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson's Disease
Shin, J.-H., Ko, H. S., Kang, H., Lee, Y., Lee, Y.-I., Pletinkova, O., Troconso, J. C., Dawson, V. L., & Dawson, T. M. (2011) · Cell · doi:10.1016/j.cell.2011.02.010 · Cited by 953 · see citing works
Diagnosis and treatment of Parkinson disease: molecules to medicine
Savitt, J. M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29178 · Cited by 649 · 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
Hunot, S., Vila, M., Teismann, P., Davis, R. J., Hirsch, É. C., Przedborski, S., RAKIC, P. T., & Flavell, R. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307453101 · Cited by 427 · see citing works
Oxidative Stress and Genetics in the Pathogenesis of Parkinson's Disease
Zhang, Y., Dawson, V. L., & Dawson, T. M. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0319 · Cited by 406 · see citing works
Behavioral phenotyping of mice in pharmacological and toxicological research
Karl, T., Pabst, R., & von Hörsten, S. (2003) · Experimental and Toxicologic Pathology · doi:10.1078/0940-2993-00301 · Cited by 327 · see citing works
Hebron, M., Lonskaya, I., & Moussa, C. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt192 · Cited by 319 · see citing works
Uptake of MPP(+) by dopamine neurons explains selectivity of parkinsonism-inducing neurotoxin, MPTP
Javitch, J. A., & Snyder, S. H. (1984) · European Journal of Pharmacology · doi:10.1016/0014-2999(84)90740-4 · Cited by 317 · see citing works
Ko, H. S., Lee, Y., Shin, J., Karuppagounder, S. S., Gadad, B. S., Koleske, A. J., Pletniková, O., Troncoso, J. C., Dawson, V. L., & Dawson, T. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006083107 · Cited by 286 · see citing works
Mahul‐Mellier, A., Fauvet, B., Gysbers, A. M., Dikiy, I., Oueslati, A., Georgeon, S., Lamontanara, A. J., Bisquertt, A., Eliezer, D., Masliah, E., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt674 · Cited by 220 · see citing works
Imam, S. Z., Zhou, Q., Yamamoto, A., Valente, A. J., Ali, S. F., Bains, M., Roberts, J. L., Kahle, P. J., Clark, R. A., & Li, S. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1833-10.2011 · Cited by 214 · see citing works
Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss
Lee, Y., Karuppagounder, S. S., Shin, J.-H., Lee, Y.-I., Ko, H. S., Swing, D., Jiang, H., Kang, S.-U., Lee, B. D., Kang, H. C., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3500 · Cited by 214 · see citing works
Therapies in Parkinsonʼs disease
Jankovic, J. J., & Poewe, W. H. (2012) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283542fc2 · Cited by 213 · see citing works
c-Abl in Neurodegenerative Disease
Schlatterer, S. D., Acker, C. M., & Davies, P. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9588-1 · Cited by 126 · see citing works
Activation of the neuronal c-Abl tyrosine kinase by amyloid-β-peptide and reactive oxygen species
Alvarez, A. R., Sandoval, P. C., Leal, N. R., Castro, P. U., & Kosik, K. S. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.06.007 · Cited by 125 · see citing works
Steegmann, J. L., Cervantes, F., le Coutre, P., Porkka, K., & Saglio, G. N. (2012) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2012.695779 · Cited by 113 · see citing works
Lane, E. L., Winkler, C., Brundin, P., & Cenci, M. A. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.11.011 · Cited by 90 · see citing works
Parkin Plays a Role in Sporadic Parkinson's Disease
Dawson, T. M., & Dawson, V. L. (2013) · Neurodegenerative Diseases · doi:10.1159/000354307 · Cited by 82 · see citing works
Imam, S. Z., Trickler, W. J., Kimura, S. H., BINIENDA, Z. K., Paule, M. G., Slikker, W., Li, S., Clark, R. A., & Ali, S. F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065129 · Cited by 76 · see citing works
Thomas, B., Mandir, A. S., West, N. C., Liu, Y., Andrabi, S. A., Stirling, W. L. H., Dawson, V. L., Dawson, T. M., & Lee, M. K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016706 · Cited by 68 · see citing works
Neuronal c-Abl Overexpression Leads to Neuronal Loss and Neuroinflammation in the Mouse Forebrain
Schlatterer, S. D., Tremblay, M. A., Acker, C. M., & Davies, P. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102025 · Cited by 65 · see citing works
Davies, A., Hayes, A. K., Knight, K., Watmough, S. J., Pirmohamed, M., & Clark, R. E. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.11.009 · Cited by 61 · see citing works
Emerging therapies for Parkinsonʼs disease
Poewe, W. H., Mahlknecht, P., & Jankovic, J. J. (2012) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283542fde · Cited by 56 · see citing works
Soverini, S., Martinelli, G., Rosti, G., Iacobucci, I., & Baccarani, M. (2012) · Pharmacogenomics · doi:10.2217/pgs.12.103 · Cited by 52 · see citing works
c-Abl in oxidative stress, aging and cancer
Li, B. (2004) · Cell Cycle · doi:10.4161/cc.4.2.1490 · Cited by 42 · see citing works
Mahul‐Mellier, A., Fauvet, B., Gysbers, A. M., Dikiy, I., Oueslati, A., Georgeon, S., Lamontanara, A. J., Bisquertt, A., Eliezer, D., Masliah, E., et al. (2014) · Qatar Foundation Annual Research Conference (ARC) · doi:10.5339/qfarc.2014.hbpp1060 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kim, S., Kwon, S.-H., Kam, T.-I., Panicker, N., Karuppagounder, S. S., Lee, S., Lee, J. H., Kim, W. R., Kook, M., Foss, C. A., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.035 · Cited by 1,397 · see citing works
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Yun, S. P., Kam, T.-I., Panicker, N., Kim, S., Oh, Y., Park, J.-S., Kwon, S.-H., Park, Y. J., Karuppagounder, S. S., Park, H., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0051-5 · Cited by 1,123 · see citing works
Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3
Mao, X., Ou, M. T., Karuppagounder, S. S., Kam, T., Yin, X., Xiong, Y., Ge, P., Umanah, G. K. E., Brahmachari, S., Shin, J., et al. (2016) · Science · doi:10.1126/science.aah3374 · Cited by 739 · see citing works
Park, J.-S., Davis, R. L., & Sue, C. M. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0829-3 · Cited by 516 · see citing works
Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease
Kam, T.-I., Mao, X., Park, H., Chou, S.-C., Karuppagounder, S. S., Umanah, G. E., Yun, S. P., Brahmachari, S., Panicker, N., Chen, R., et al. (2018) · Science · doi:10.1126/science.aat8407 · Cited by 476 · see citing works
Lang, A. E., & Espay, A. J. (2018) · Movement Disorders · doi:10.1002/mds.27360 · Cited by 374 · see citing works
Emerging therapies in Parkinson disease — repurposed drugs and new approaches
Elkouzi, A., Vedam‐Mai, V., Eisinger, R. S., & Okun, M. S. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0155-7 · Cited by 304 · see citing works
Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies
Pagan, F., Hebron, M., Valadez, E. H., Torres-Yaghi, Y., Huang, X., Mills, R. R., Wilmarth, B. M., Howard, H., Dunn, C., Carlson, A., et al. (2016) · Journal of Parkinson’s Disease · doi:10.3233/jpd-160867 · Cited by 265 · see citing works
Goyal, V., & Radhakrishnan, D. M. (2018) · Neurology India · doi:10.4103/0028-3886.226451 · Cited by 249 · see citing works
PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics
Ying, H., Chen, Q., Zhang, W., Zhang, H., Ma, Y., Zhang, S., Fang, J., & Yu, C.-H. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7641 · Cited by 238 · see citing works
Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases
Djajadikerta, A., Keshri, S., Tanasa, M. P., Prestil, R., Ryan, L., & Rubinsztein, D. C. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.035 · Cited by 238 · see citing works
Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration
Brahmachari, S., Ge, P., Lee, S. H., Kim, D., Karuppagounder, S. S., Kumar, M., Mao, X., Shin, J. H., Lee, Y., Pletniková, O., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85456 · Cited by 199 · see citing works
Therapeutic landscape for Batten disease: current treatments and future prospects
Johnson, T. B., Cain, J. T., White, K. A., Ramirez‐Montealegre, D., Pearce, D. A., & Weimer, J. M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0138-8 · Cited by 187 · see citing works
Pagan, F. L., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Anjum, M., Arellano, J., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4200 · Cited by 185 · see citing works
Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic
Sardi, S. P., Cedarbaum, J. M., & Brundin, P. (2018) · Movement Disorders · doi:10.1002/mds.27414 · Cited by 175 · see citing works
Recent developments in the treatment of Parkinson's Disease
Stoker, T. B., & Barker, R. A. (2020) · F1000Research · doi:10.12688/f1000research.25634.1 · Cited by 168 · see citing works
Zhang, K., Zhu, S., Li, J., Jiang, T., Feng, L., Pei, J., Wang, G., Ouyang, L., & Liu, B. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.02.016 · Cited by 158 · see citing works
Simuni, T., Fiske, B., Merchant, K., Coffey, C. S., Klingner, E., Caspell-Garcia, C., Lafontant, D.-E., Matthews, H., Wyse, R. K., Brundin, P., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4725 · Cited by 149 · see citing works
Pillaiyar, T., Meenakshisundaram, S., Manickam, M., & Sankaranarayanan, M. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112275 · Cited by 140 · see citing works
Yun, S. P., Kim, D., Kim, S., Kim, S., Karuppagounder, S. S., Kwon, S., Lee, S., Kam, T., Lee, S.-H., Ham, S., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0233-5 · Cited by 133 · see citing works
Multifunctional Abl kinases in health and disease
Khatri, A., Wang, J., & Pendergast, A. M. (2016) · Journal of Cell Science · doi:10.1242/jcs.175521 · Cited by 133 · see citing works
Targeting mitophagy in Parkinson's disease
Clark, E. H., de la Torre, A. V., Hoshikawa, T., & Briston, T. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.014294 · Cited by 128 · see citing works
Amelioration of pathologic α-synuclein-induced Parkinson’s disease by irisin
Kam, T.-I., Park, H., Chou, S.-C., Van Vranken, J. G., Mittenbühler, M. J., Kim, H., A, M., Choi, Y. R., Biswas, D., Wang, J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204835119 · Cited by 125 · see citing works
Self-citationNilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer’s Disease
Turner, R. S., Hebron, M. L., Lawler, A., Mundel, E. E., Yusuf, N., Starr, J. N., Anjum, M., Pagan, F., Torres‐Yaghi, Y., Shi, W., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25775 · Cited by 126 · see citing works
PAAN/MIF nuclease inhibition prevents neurodegeneration in Parkinson’s disease
Park, H., Kam, T., Peng, H., Chou, S.-C., Mehrabani-Tabari, A. A., Song, J., Yin, X., Karuppagounder, S. S., Umanah, G. K. E., Rao, A., et al. (2022) · Cell · doi:10.1016/j.cell.2022.04.020 · Cited by 125 · see citing works
Parisi, D., Adasme, M. F., Sveshnikova, A. N., Bolz, S. N., Moreau, Y., & Schroeder, M. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.04.004 · Cited by 122 · see citing works
Pagán, F., Hebron, M. L., Wilmarth, B., Torres-Yaghi, Y. A., Lawler, A., Mundel, E. E., Yusuf, N., Starr, N. J., Arellano, J., Howard, H. H., et al. (2019) · Pharmacology Research & Perspectives · doi:10.1002/prp2.470 · Cited by 117 · see citing works
Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson’s disease
Sarkar, S., Nguyen, H. M., Malovic, E., Luo, J. D., Langley, M. R., Palanisamy, B. N., Singh, N., Manne, S., Neal, M. P., Gabrielle, M., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136174 · Cited by 114 · see citing works
Clark, I. A., & Vissel, B. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0708-2 · Cited by 123 · see citing works
The Vicious Cycle Between α ‐Synuclein Aggregation and Autophagic‐Lysosomal Dysfunction
Bellomo, G., Paciotti, S., Gatticchi, L., & Parnetti, L. (2019) · Movement Disorders · doi:10.1002/mds.27895 · Cited by 114 · see citing works
α-Synuclein pathology as a target in neurodegenerative diseases
Park, H.-J., Kam, T., Dawson, V. L., & Dawson, T. M. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-01043-w · Cited by 113 · see citing works
Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson's Disease
Jasutkar, H. G., Oh, S. E., & Mouradian, M. M. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000133 · Cited by 102 · see citing works
c-Abl and Parkinson’s Disease: Mechanisms and Therapeutic Potential
Brahmachari, S., Karuppagounder, S. S., Ge, P., Lee, S., Dawson, V. L., Dawson, T. M., & Ko, H. S. (2017) · Journal of Parkinson s Disease · doi:10.3233/jpd-171191 · Cited by 101 · see citing works
La Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E. C., Cutuli, D., Cauzzi, E., Marino, R., Viscomi, M. T., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102031 · Cited by 98 · see citing works
“neurodegenerative diseases, including PD and AD (Gonfloni et al., 2012; Hebron et al., 2013a; Imam et al., 2011; Jing et al., 2009; Karuppagounder et al., 2014; Ko et al., 2010; Lindholm et al., 2016; Schlatterer et al., 2011).”
BackgroundResultBiological and Clinical Implications of Comorbidities in Parkinson’s Disease
Santiago, J. A., Bottero, V., & Potashkin, J. A. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00394 · Cited by 95 · see citing works
Graph Neural Networks in Modern AI-Aided Drug Discovery
Zhang, O., Lin, H., Zhang, X., Wang, X., Wu, Z., Ye, Q., Zhao, W., Wang, J., Ying, K., Kang, Y., et al. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00461 · Cited by 103 · see citing works
Expanding the role of proteasome homeostasis in Parkinson’s disease: beyond protein breakdown
Bi, M., Du, X., Jiao, Q., Chen, X., & Jiang, H. F. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03441-0 · Cited by 87 · see citing works
Alpha and Beta Synucleins: From Pathophysiology to Clinical Application as Biomarkers
Barba, L., Paoletti, F. P., Bellomo, G., Gaetani, L., Halbgebauer, S., Oeckl, P., Otto, M., & Parnetti, L. (2022) · Movement Disorders · doi:10.1002/mds.28941 · Cited by 88 · see citing works
Pirooznia, S. K., Yuan, C., Khan, M. R., Karuppagounder, S. S., Wang, L., Xiong, Y., Kang, S. U., Lee, Y., Dawson, V. L., & Dawson, T. M. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00363-x · Cited by 88 · see citing works
Parkin Regulation and Neurodegenerative Disorders
Zhang, C., Hang, L., Yao, T., & Lim, K. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00248 · Cited by 82 · see citing works
Zhou, L., Zhang, Q., Zhang, P., Sun, L., Peng, C., Yuan, Z., & Cheng, J. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.524 · Cited by 84 · see citing works
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
Lee, S., Kim, S., Park, Y. J., Yun, S. P., Kwon, S., Kim, D., Kim, D.-Y., Shin, J. S., Cho, D. J., Lee, G. Y., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy143 · Cited by 82 · see citing works
MicroRNA-7 facilitates the degradation of alpha-synuclein and its aggregates by promoting autophagy
Choi, D. C., Yoo, M., Kabaria, S., & Junn, E. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.05.009 · Cited by 80 · see citing works
c-Abl–p38α signaling plays an important role in MPTP-induced neuronal death
Wu, R., Chen, H., Ma, J., He, Q., Huang, Q., Liu, Q., Li, M., & Yuan, Z. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.135 · Cited by 82 · see citing works
Active immunization therapies for Parkinson's disease and multiple system atrophy
Schneeberger, A., Tierney, L., & Mandler, M. (2015) · Movement Disorders · doi:10.1002/mds.26377 · Cited by 81 · see citing works
Autophagy regulates MAVS signaling activation in a phosphorylation-dependent manner in microglia
Cheng, J., Liao, Y., Xiao, L., Wu, R., Zhao, S., Chen, H., Hou, B., Zhang, X., Liang, C., Xu, Y., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.121 · Cited by 79 · see citing works
Lawana, V., Singh, N., Sarkar, S., Charli, A., Jin, H., Anantharam, V., Kanthasamy, A. G., & Kanthasamy, A. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9746-5 · Cited by 73 · see citing works
Neurotransmission systems in Parkinson’s disease
Moghaddam, H. S., Zare-Shahabadi, A., Rahmani, F., & Rezaei, N. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0068 · Cited by 76 · see citing works
He, J., Xu, L., Yang, S., Li, Y., Lin, X., Xiu, M., Li, X., & Liu, Y. (2021) · Food & Function · doi:10.1039/d1fo00847a · Cited by 72 · see citing works
Scott, L., Dawson, V., & Dawson, T. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.008 · Cited by 67 · see citing works
Activation of the ATF2/CREB-PGC-1α pathway by metformin leads to dopaminergic neuroprotection
Kang, H., Khang, R., Ham, S., Jeong, G. R., Kim, H., Jo, M., Lee, B. D., Lee, Y. I., Jo, A., Park, C., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18122 · Cited by 70 · see citing works
Vargas, L. M., Cerpa, W. F., Muñoz, F. J., Zanlungo, S., & Alvarez, A. R. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.01.023 · Cited by 69 · see citing works
Brahmachari, S., Lee, S., Kim, S., Yuan, C.-Q., Karuppagounder, S. S., Ge, P., Shi, R., Kim, E. J., Liu, A. C. H., Kim, D., et al. (2019) · Brain : a journal of neurology · doi:10.1093/brain/awz172 · Cited by 62 · see citing works
PARIS farnesylation prevents neurodegeneration in models of Parkinson’s disease
Jo, A., Lee, Y., Kam, T., Kang, S.-U., Neifert, S., Karuppagounder, S. S., Khang, R., Kang, H., Park, H., Chou, S.-C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aax8891 · Cited by 66 · see citing works
α-Synucleinopathy associated c-Abl activation causes p53-dependent autophagy impairment
Karim, M. R., Liao, E. E., Kim, J., Meints, J. P., Martínez, H., Pletniková, O., Troncoso, J. C., & Lee, M. K. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00364-w · Cited by 66 · see citing works
Xu, Y., Cui, C., Sun, M., Zhu, Y., Chu, M., Shi, Y., Lin, S. L., Yang, X., & Shen, Y. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26010 · Cited by 65 · see citing works
Activation mechanisms of the E3 ubiquitin ligase parkin
Panicker, N., Dawson, V. L., & Dawson, T. M. (2017) · Biochemical Journal · doi:10.1042/bcj20170476 · Cited by 63 · see citing works
Parkinson's Disease Modification Through Abl Kinase Inhibition: An Opportunity
Werner, M. H., & Olanow, C. W. (2021) · Movement Disorders · doi:10.1002/mds.28858 · Cited by 60 · see citing works
Membrane interactions of intrinsically disordered proteins: The example of alpha-synuclein
Das, T., & Eliezer, D. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.05.001 · Cited by 61 · see citing works
Drug Repurposing in Parkinson’s Disease
Athauda, D. S., & Foltynie, T. (2018) · CNS Drugs · doi:10.1007/s40263-018-0548-y · Cited by 59 · see citing works
A Stage-Based Approach to Therapy in Parkinson’s Disease
Carrarini, C., Russo, M., Dono, F., Pietro, M. D., Rispoli, M. G., Stefano, V. D., Ferri, L., Barbone, F., Vitale, M., Thomas, A., et al. (2019) · Biomolecules · doi:10.3390/biom9080388 · Cited by 58 · see citing works
Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
Benn, C., & Dawson, L. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00242 · Cited by 57 · see citing works
Azeggagh, S., & Berwick, D. C. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15575 · Cited by 56 · see citing works
Structure-based drug repositioning: Potential and limits
Adasme, M. F., Parisi, D., Sveshnikova, A. N., & Schroeder, M. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.01.010 · Cited by 55 · see citing works
Approaches to Disease Modification for Parkinson's Disease: Clinical Trials and Lessons Learned
Hung, A. Y., & Schwarzschild, M. A. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00964-w · Cited by 52 · see citing works
Karuppagounder, S. S., Xiong, Y., Lee, Y., Lawless, M. C., Kim, D., Nordquist, E., Martin, I., Ge, P., Brahmachari, S., Jhaldiyal, A., et al. (2016) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2016.01.007 · Cited by 52 · see citing works
c-Abl Inhibitors Enable Insights into the Pathophysiology and Neuroprotection in Parkinson’s Disease
Lindholm, D., Pham, D. D., Cascone, A., Eriksson, O., Wennerberg, K., & Saarma, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00254 · Cited by 52 · see citing works
Lewandowski, S. A., Fredriksson, L., Lawrence, D. A., & Eriksson, U. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.07.016 · Cited by 52 · see citing works
Attia, G. M., Elmansy, R. A., & Elsaed, W. M. (2019) · Folia Neuropathologica · doi:10.5114/fn.2019.84423 · Cited by 51 · see citing works
Jung, J. H., Jung, D., Kim, H., Lee, H., Kang, S., Srivastava, S., Yun, M., & Kim, S. (2018) · Oncogene · doi:10.1038/s41388-018-0225-0 · Cited by 48 · see citing works
c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder
Contreras, P. S., Tapía, P., González-Hódar, L., Peluso, I., Soldati, C., Napolitano, G., Matarese, M., Heras, M. L., Valls, C., Martinez, A. N., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101691 · Cited by 46 · see citing works
Loss of mitochondrial protein CHCHD10 in skeletal muscle causes neuromuscular junction impairment.
Xiao, Y.-T., Zhang, J.-M., Shu, X.-Q., Bai, L., Xu, W., Wang, A.-L., Chen, A., Tu, W.-Y., Wang, J.-W., Zhang, K.-J., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddz154 · Cited by 43 · see citing works
Protein clearance strategies for disease intervention
Hommen, F., Bilican, S., & Vı́lchez, D. (2021) · Journal of Neural Transmission · doi:10.1007/s00702-021-02431-y · Cited by 44 · see citing works
Liu, X., Liu, W., Wang, C., Chen, Y., Liu, P., Hayashi, T., Mizuno, K., Hattori, S., Fujisaki, H., & Takashi, I. (2021) · Physiology & Behavior · doi:10.1016/j.physbeh.2021.113510 · Cited by 44 · see citing works
Alpha synuclein post translational modifications: potential targets for Parkinson’s disease therapy?
Brembati, V., Faustini, G., Longhena, F., & Bellucci, A. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1197853 · Cited by 42 · see citing works
Lewy body dementia promotion by air pollutants
Zhang, X., Liu, H., Wu, X., Jia, L., Gadhave, K., Wang, L., Zhang, K., Li, H., Chen, R., Kumbhar, R., et al. (2025) · Science · doi:10.1126/science.adu4132 · Cited by 46 · see citing works
Ensembled machine learning framework for drug sensitivity prediction
Sharma, A., & Rani, R. (2019) · IET Systems Biology · doi:10.1049/iet-syb.2018.5094 · Cited by 40 · see citing works
Diesel Exhaust Extract Exposure Induces Neuronal Toxicity by Disrupting Autophagy
Barnhill, L. M., Khuansuwan, S., Juárez-Serrano, D., Murata, H., Araujo, J. A., & Bronstein, J. M. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa055 · Cited by 39 · see citing works
Therapeutic strategies in Parkinson's disease: what we have learned from animal models
Valadas, J. S., Vos, M. H., & Verstreken, P. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12577 · Cited by 38 · see citing works
The Challenge of Disease-Modifying Therapies in Parkinson’s Disease: Role of CSF Biomarkers
Paoletti, F. P., Gaetani, L., & Parnetti, L. (2020) · Biomolecules · doi:10.3390/biom10020335 · Cited by 38 · see citing works
Angelopoulou, E., Paudel, Y. N., Villa, C., Shaikh, M. F., & Piperi, C. (2020) · Biology · doi:10.3390/biology9040086 · Cited by 40 · see citing works
Genotype-driven therapeutic developments in Parkinson’s disease
Prasuhn, J., & Brüggemann, N. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00281-8 · Cited by 38 · see citing works
Protein Kinases and Parkinson’s Disease
Mehdi, S. J., Rosas-Hernández, H., Cuevas, E., Lantz, S. M., Barger, S. W., Sarkar, S., Paule, M. G., Ali, S. F., & Imam, S. Z. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091585 · Cited by 38 · see citing works
Xiao, H., Han, B., Zhao, Y., Li, G., Wang, T., He, J., Du, W., Cao, X., Gan, J., Wang, Z., et al. (2022) · Nutrients · doi:10.3390/nu14173508 · Cited by 37 · see citing works
Nilotinib – Differentiating the Hope from the Hype
Wyse, R. K. H., Brundin, P., & Sherer, T. (2016) · Journal of Parkinson s Disease · doi:10.3233/jpd-160904 · Cited by 36 · see citing works
New Frontiers in Parkinson's Disease: From Genetics to the Clinic
Shihabuddin, L. S., Brundin, P., Greenamyre, J. T., Stephenson, D. T., & Sardi, S. P. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1666-18.2018 · Cited by 36 · see citing works
Wu, J., Xu, X., Li, Z., Mo, J., Jin, X., & Bao, Y. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108025 · Cited by 36 · see citing works
Liao, X., Qin, G., Liu, Z., Ren, J., & Qu, X. (2023) · Small · doi:10.1002/smll.202306760 · Cited by 35 · see citing works
Estrada, L. D., Chamorro, D., Yañez, M. J., González, M., Leal, N. R., Rommy von Bernhardi, M., Dulcey, A. E., Marugán, J., Ferrer, M., Soto, C. A., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151087 · Cited by 35 · see citing works
EphA2 contributes to disruption of the blood-brain barrier in cerebral malaria
Darling, T. K., Mimche, P. N., Bray, C., Umaru, B. A., Brady, L. M., Stone, C., Moukoko, C. E. E., Lane, T. E., Ayong, L. S., & Lamb, T. J. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008261 · Cited by 35 · see citing works
Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection
Pirooznia, S. K., Rosenthal, L. S., Dawson, V. L., & Dawson, T. M. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000189 · Cited by 36 · see citing works
Karuppagounder, S. S., Wang, H., Kelly, T., Rush, R., Nguyen, R. Q., Bisen, S. S., Yamashita, Y., Sloan, N., Dang, B., Sigmon, A., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abp9352 · Cited by 35 · see citing works
Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis
Peikert, K., Federti, E., Mattè, A., Constantin, G., Pietronigro, E. C., Fabene, P. F., Defilippi, P., Turco, E., Gallo, F. D., Pucci, P., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01181-y · Cited by 34 · see citing works
Mitophagy in Parkinson's disease: From pathogenesis to treatment target
Dernie, F. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104756 · Cited by 33 · see citing works
Oda, W., Fujita, Y., Baba, K., Mochizuki, H., Niwa, H., & Yamashita, T. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03469-2 · Cited by 33 · see citing works
Sun, R., Song, Y., Li, S., Ma, Z., Deng, X., Fu, Q., Qu, R., & Ma, S. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1063-9 · Cited by 33 · see citing works
Structure-based design and characterization of Parkin-activating mutations
Stevens, M., Croteau, N., Eldeeb, M. A., Antico, O., Zeng, Z. W., Toth, R. L., Durcan, T. M., Springer, W., Fon, E. A., Muqit, M. M. K., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202201419 · Cited by 32 · see citing works
The Role of c-Abl Tyrosine Kinase in Brain and Its Pathologies
Motaln, H., & Rogelj, B. (2023) · Cells · doi:10.3390/cells12162041 · Cited by 32 · see citing works
Khuansuwan, S., Barnhill, L. M., Cheng, S., & Bronstein, J. M. (2019) · Autophagy · doi:10.1080/15548627.2019.1580511 · Cited by 32 · see citing works
- Authors
- Karuppagounder, S. S., Brahmachari, S., Lee, Y., Dawson, V. L., Dawson, T. M., & Ko, H. S.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Dawson, Ted M.
- Ko, Han Seok
- ORCID
- Venue
- Scientific Reports
- Published
- 2014-05-02
- Volume
- 4
- Issue
- 1
- Pages
- 4874-4874
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4007078
- OpenAlex
- W2017715011
- Cited by
- 264
- References
- 28
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 19 · 2023: 21 · 2022: 21 · 2021: 25 · 2020: 45 · 2019: 28 · 2018: 28 · 2017: 17 · 2016: 20 · 2015: 4 · 2014: 3
- FWCI
- 9.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Adrienne Helis Malvin Medical Research Foundation
- JPB Foundation
- Johns Hopkins University
- Diana Helis Henry Medical Research Foundation
- National Institutes of Health (NS38377)
- Samsung
- National Institute of Neurological Disorders and Stroke (NS 38377, P50NS038377)
- 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
- nilotinib, Parkinson's disease, dopaminergic neuron loss, MPTP-induced neurotoxicity, Parkin, Paris, AIMP2, tyrosine phosphorylation, neuroprotection
- MeSH terms
- Animals, Behavior, Animal, Blood-Brain Barrier, Brain, Disease Models, Animal, Enzyme Activation, Male, Parkinson Disease, Phosphorylation, Pyrimidines, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Proto-Oncogene Proteins c-abl, Neuroprotective Agents, Ubiquitin-Protein Ligases, Mice, Dopaminergic Neurons
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
