RTP801 Is Induced in Parkinson's Disease and Mediates Neuron Death by Inhibiting Akt Phosphorylation/Activation
Open accessAbstract
Previously, we reported that RTP801, a stress regulated protein, is induced in multiple cellular models of Parkinson's disease (PD), in an animal model of PD and in dopaminergic neurons of PD patients. In cellular PD models, RTP801 is both sufficient and necessary for death. We further showed that RTP801 and PD mimetics such as 6-OHDA trigger neuron death by suppressing activation of the key kinase mammalian target of rapamycin (mTOR). Here, we report that as a consequence of mTOR signaling blockade, 6-OHDA suppresses the phosphorylation and activation of Akt, a major supporter of neuron survival. This effect is mediated by RTP801 and appears to underlie neuron death induced by 6-OHDA. Examination of postmortem dopaminergic neurons reveals a consistent depletion of phospho-Akt, but not of total Akt in PD patients. These observations support a sequential mechanism in which PD-associated stresses induce RTP801, suppress mTOR signaling, deplete phosphorylated/activated Akt and permit neuron degeneration and death.
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?
Lower expression of AKT in dopaminergic neurons of PD patients than in normal people.
“Previous results indicated that a lower expression of AKT in dopaminergic neurons of PD patients than that in normal people (Malagelada et al. 2008)”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Malagelada et al. 2008
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
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · see citing works
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80405-5 · Cited by 5,689 · see citing works
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
Self-citationInhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244 · see citing works
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 2,985 · see citing works
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 2,974 · see citing works
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665 · see citing works
Regulation of neuronal survival by the serine-threonine protein kinase Akt
Dudek, H., Datta, S. R., Franke, T. F., Birnbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., & Greenberg, M. E. (1997) · Science · doi:10.1126/science.275.5300.661 · Cited by 2,436 · see citing works
Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347 · see citing works
Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt
del Peso, L., González‐García, M., Page, C., Herrera, R., & Núñez, G. (1997) · Science · doi:10.1126/science.278.5338.687 · Cited by 2,213 · see citing works
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097 · see citing works
Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action
Hara, K., Maruki, Y., Long, X., Yoshino, K.-I., Oshiro, N., Sujuti, H., Tokunaga, C., Avruch, J., & Yonezawa, K. (2002) · Cell · doi:10.1016/s0092-8674(02)00833-4 · Cited by 1,810 · see citing works
PI3K: Downstream AKTion Blocks Apoptosis
Franke, T. F., Kaplan, D. R., & Cantley, L. C. (1997) · Cell · doi:10.1016/s0092-8674(00)81883-8 · Cited by 1,692 · see citing works
Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate
Franke, T. F., Kaplan, D., Cantley, L., & Toker, A. (1997) · Science · doi:10.1126/science.275.5300.665 · Cited by 1,609 · see citing works
Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S. Y., Huang, Q., Qin, J., & Su, B. (2006) · Cell · doi:10.1016/j.cell.2006.08.033 · Cited by 1,407 · see citing works
Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384 · see citing works
A transforming mutation in the pleckstrin homology domain of AKT1 in cancer
Carpten, J. D., Faber, A. L., Horn, C. L., Donoho, G. P., Briggs, S., Robbins, C. M., Hostetter, G. H., Boguslawski, S. J., Moses, T. Y., Savage, S., et al. (2007) · Nature · doi:10.1038/nature05933 · Cited by 1,291 · see citing works
Brunet, A., Datta, S. R., & Greenberg, M. E. (2001) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00211-7 · Cited by 1,193 · see citing works
Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease.
Anglade, P., Vyas, S., Javoy-Agid, F., Herrero, M. T., Michel, P. P., Marquez, J., Prigent, A., Ruberg, M., Hirsch, É. C., & Agid, Y. (1997) · PubMed · Cited by 1,045 · see citing works
Kulik, G., Klippel, A., & Weber, M. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1595 · Cited by 1,033 · see citing works
DeYoung, M. P., Horak, P., Sofer, A., Sgroi, D., & Ellisen, L. W. (2008) · Genes & Development · doi:10.1101/gad.1617608 · Cited by 710 · see citing works
Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways
Kumar, V., Zhang, M.-X., Swank, M. W., Kunz, J., & Wu, G.-Y. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2284-05.2005 · Cited by 588 · see citing works
Jaworski, J., Spangler, S. A., Seeburg, D. P., Hoogenraad, C. C., & Sheng, M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2270-05.2005 · Cited by 577 · see citing works
Crowder, R. J., & Freeman, R. S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02933.1998 · Cited by 575 · see citing works
Ryu, E. J., Harding, H. P., Angelastro, J. M., Vitolo, O. V., Ron, D., & Greene, L. A. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10690.2002 · Cited by 572 · see citing works
Self-citationPhosphorylation of Mammalian Target of Rapamycin (mTOR) at Ser-2448 IsMediated by p70S6 Kinase
Chiang, G. G., & Abraham, R. T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501707200 · Cited by 562 · see citing works
Shoshani, T., Faerman, A., Mett, I., Zelin, E., Tenne, T., Gorodin, S., Moshel, Y., Elbaz, S., Budanov, A., Chajut, A., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2283-2293.2002 · Cited by 546 · see citing works
Ellisen, L. W., Ramsayer, K. D., Johannessen, C. M., Yang, A., Beppu, H., Minda, K., Oliner, J. D., McKeon, F., & Haber, D. A. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00706-2 · Cited by 474 · see citing works
Orimo, S., Uchihara, T., Nakamura, A., Mori, F., Kakita, A., Wakabayashi, K., & Takahashi, H. (2007) · Brain · doi:10.1093/brain/awm302 · Cited by 462 · see citing works
Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1
Sofer, A., Lei, K., Johannessen, C. M., & Ellisen, L. W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.5834-5845.2005 · Cited by 449 · see citing works
Role of mTOR in physiology and pathology of the nervous system
Swiech, L., Perycz, M., Malik, A., & Jaworski, J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.015 · Cited by 338 · see citing works
Yang, Y., Gehrke, S., Haque, M. E., Imai, Y., Kosek, J. C., Yang, L., Beal, M. F., Nishimura, I., Wakamatsu, K., Ito, S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504610102 · Cited by 338 · see citing works
Raf and Akt Mediate Distinct Aspects of Sensory Axon Growth
Markus, A., Zhong, J., & Snider, W. D. (2002) · Neuron · doi:10.1016/s0896-6273(02)00752-3 · Cited by 327 · see citing works
PRAS40 and PRR5-Like Protein Are New mTOR Interactors that Regulate Apoptosis
Thedieck, K., Polak, P., Kim, M. L., Molle, K. D., Cohen, A., Jenö, P., Arrieumerlou, C., & Hall, M. N. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001217 · Cited by 290 · see citing works
Activated Phosphatidylinositol 3-Kinase and Akt Kinase Promote Survival of Superior Cervical Neurons
Philpott, K. L., McCarthy, M. J., Klippel, A., & Rubin, L. L. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.3.809 · Cited by 242 · see citing works
Corradetti, M. N., Inoki, K., & Guan, K.-L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c400557200 · Cited by 237 · see citing works
Malagelada, C., Ryu, E. J., Biswas, S. C., Jackson-Lewis, V. R., & Greene, L. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3292-06.2006 · Cited by 189 · see citing works
Self-citationMorphometry of the human substantia nigra in ageing and Parkinson’s disease
Rudow, G. L., O’Brien, R., Savonenko, A. V., Resnick, S. M., Zonderman, A. B., Pletniková, O., Marsh, L., Dawson, T. M., Crain, B. J., West, M. J., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0352-8 · Cited by 184 · 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
Neuronal macroautophagy: From development to degeneration
Boland, B., & Nixon, R. A. (2006) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2006.08.009 · Cited by 156 · see citing works
Wang, Z., Malone, M. H., Thomenius, M. J., Zhong, F., Xu, F., & Distelhorst, C. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303723200 · Cited by 144 · see citing works
REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase
Schwarzer, R., Tondera, D., Arnold, W., Giese, K., Klippel, A., & Kaufmann, J. (2004) · Oncogene · doi:10.1038/sj.onc.1208236 · Cited by 129 · see citing works
Inhibition of Oxygen-Induced Retinopathy in RTP801-Deficient Mice
Brafman, A., Mett, I. L., Shafir, M., Gottlieb, H., Damari, G. M., Gozlan-Kelner, S., Vishnevskia‐Dai, V., Skaliter, R., Einat, P., Faerman, A., et al. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0052 · Cited by 128 · see citing works
Analysis of gene expression changes in a cellular model of Parkinson disease
Ryu, E. J., Angelastro, J. M., & Greene, L. A. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.08.016 · Cited by 95 · see citing works
Self-citationFKHRL1 and its homologs are new targets of nerve growth factor Trk receptor signaling
Zheng, W., Kar, S., & Quirion, R. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00783.x · Cited by 89 · see citing works
Invited Article: Changing concepts in Parkinson disease
Marras, C., & Lang, A. E. (2008) · Neurology · doi:10.1212/01.wnl.0000312515.52545.51 · Cited by 85 · see citing works
A Golgi study of human locus coeruleus in normal brains and in Parkinson's disease
Patt, S., & Gerhard, L. (1993) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1993.tb00480.x · Cited by 64 · see citing works
Medical treatment of Parkinson’s disease
Fahn, S. (1998) · Journal of Neurology · doi:10.1007/pl00007742 · Cited by 38 · 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
Self-citation
Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Heras-Sandoval, D., Pérez-Rojas, J. M., Hernández-Damián, J., & Pedraza-Chaverri, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.08.019 · Cited by 1,091 · see citing works
Human iPSC-based modeling of late-onset disease via progerin-induced aging
Miller, J. D., Ganat, Y. M., Kishinevsky, S., Bowman, R. L., Liu, B., Tu, E. Y., Mandal, P. K., Vera, E., Shim, J.-W., Kriks, S., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.006 · Cited by 777 · see citing works
Fighting neurodegeneration with rapamycin: mechanistic insights
Bové, J., Martínez‐Vicente, M., & Vila, M. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3068 · Cited by 525 · see citing works
Cooper, O., Seo, H., Andrabi, S., Guardia-Laguarta, C., Graziotto, J., Sundberg, M., McLean, J. R., Carrillo-Reid, L., Xie, Z., Osborn, T., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003985 · Cited by 508 · see citing works
The Role of PI3K/Akt and ERK in Neurodegenerative Disorders
Nand, S., Dilnashin, H., Birla, H., Singh, S. S., Zahra, W., Singh, B. K., Singh, S. P., & Singh, S. P. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-0003-y · Cited by 480 · see citing works
Rapamycin Protects against Neuron Death inIn VitroandIn VivoModels of Parkinson's Disease
Malagelada, C., Jin, Z. H., Jackson-Lewis, V. R., Przedborski, S., & Greene, L. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3944-09.2010 · Cited by 458 · see citing works
Self-citationAthauda, D., & Foltynie, T. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.01.013 · Cited by 383 · see citing works
mTOR in Brain Physiology and Pathologies
Bockaert, J., & Marin, P. (2015) · Physiological Reviews · doi:10.1152/physrev.00038.2014 · Cited by 360 · see citing works
Insulin resistance and Parkinson’s disease: A new target for disease modification?
Athauda, D. S., & Foltynie, T. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.10.001 · Cited by 333 · see citing works
mTORC2 controls actin polymerization required for consolidation of long-term memory
Huang, W., Zhu, P. J., Zhang, S., Zhou, H., Stoica, L., Galiano, M., Krnjević, K., Roman, G., & Costa-Mattioli, M. (2013) · Nature Neuroscience · doi:10.1038/nn.3351 · Cited by 307 · see citing works
The Therapeutic Potential of Metformin in Neurodegenerative Diseases
Rotermund, C., Machetanz, G., & Fitzgerald, J. C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00400 · Cited by 310 · see citing works
Kopp, K. O., Glotfelty, E. J., Li, Y., & Greig, N. H. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106550 · Cited by 298 · see citing works
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · 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
Self-citationGlycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease
Golpich, M., Amini, E., Hemmati, F., Ibrahim, N. M., Rahmani, B., Mohamed, Z., Raymond, A. A., Dargahi, L., Ghasemi, R., & Ahmadiani, A. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.03.010 · Cited by 276 · see citing works
Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases
Fão, L., Mota, S. I., & Rego, A. C. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100942 · Cited by 270 · see citing works
Inhibition of mTOR Signaling in Parkinson’s Disease Prevents l -DOPA–Induced Dyskinesia
Santini, E., Heiman, M., Greengard, P., Valjent, E., & Fisone, G. (2009) · Science Signaling · doi:10.1126/scisignal.2000308 · Cited by 256 · see citing works
Athauda, D. S., Gulyani, S., Karnati, H. K., Li, Y., Tweedie, D., Mustapić, M., Chawla, S., Chowdhury, K., Skene, S. S., Greig, N. H., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.4304 · Cited by 259 · see citing works
Selvaraj, S., Sun, Y., Watt, J. A., Wang, S., Lei, S., Birnbaumer, L., & Singh, B. B. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61332 · Cited by 245 · see citing works
Neuroprotective actions of sex steroids in Parkinson’s disease
Bourque, M., Dluzen, D. E., & Paolo, T. D. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.04.014 · Cited by 239 · see citing works
The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson's Disease Dementia
Yang, L., Wang, H., Liu, L., & Xie, A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00073 · Cited by 228 · see citing works
Akt signal transduction dysfunction in Parkinson's disease
Timmons, S., Coakley, M. F., Moloney, A. M., & Neill, C. O. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.09.055 · Cited by 192 · see citing works
Ghosh, A., Tyson, T., George, S., Hildebrandt, E. N., Steiner, J. A., Madaj, Z., Schulz, E., Machiela, E., McDonald, W. G., Galvis, M. L. E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aag2210 · Cited by 187 · see citing works
The Chemical Biology of Ferroptosis in the Central Nervous System
Ratan, R. R. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.03.007 · Cited by 181 · see citing works
Arab, H. H., Safar, M. M., & Shahin, N. N. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00722 · Cited by 180 · see citing works
Tonges, L., Frank, T., Tatenhorst, L., Saal, K. A., Koch, J. C., Szego, E. M., Bahr, M., Weishaupt, J. H., & Lingor, P. (2012) · Brain · doi:10.1093/brain/aws254 · Cited by 176 · see citing works
Xu, Y., Liu, C., Chen, S., Ye, Y., Guo, M., Ren, Q., Liu, L., Zhang, H., Xu, C., Zhou, Q., et al. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.04.009 · Cited by 171 · see citing works
Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas
Área-Gómez, E., Guardia‐Laguarta, C., Schon, E. A., & Przedborski, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci120848 · Cited by 169 · see citing works
DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway
Aleyasin, H., Rousseaux, M. W. C., Marcogliese, P. C., Hewitt, S. J., Irrcher, I., Joselin, A. P., Parsanejad, M., Kim, R. H., Rizzu, P., Callaghan, S. M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914876107 · Cited by 168 · see citing works
Reglodi, D., Renaud, J., Tamas, A., Tizabi, Y., Socías, S. B., Del-Bel, E., & Raisman-Vozari, R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.10.004 · Cited by 162 · see citing works
Rai, S. N., Birla, H., Singh, S. S., Zahra, W., Patil, R. R., Jadhav, J. P., Gedda, M. R., & Singh, S. P. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00421 · Cited by 161 · see citing works
Mammalian Target of Rapamycin: Hitting the Bull′s‐Eye for Neurological Disorders
Chong, Z. Z., Shang, Y., Zhang, L., Wang, S., & Maiese, K. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.6.14787 · Cited by 149 · see citing works
Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice
Matak, P., Matak, A., Moustafa, S. M., Aryal, D. K., Benner, E. J., Wetsel, W. C., & Andrews, N. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1519473113 · Cited by 133 · see citing works
ATF4 protects against neuronal death in cellular PD models by maintaining levels of parkin
Sun, X., Liu, J., Crary, J. F., Malagelada, C., Sulzer, D., Greene, L., & Levy, O. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2292-12.2013 · Cited by 123 · see citing works
Self-citationTejeda, G., & Díaz-Guerra, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020268 · Cited by 126 · see citing works
Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease
Mortiboys, H., Aasly, J. O., & Bandmann, O. (2013) · Brain · doi:10.1093/brain/awt224 · Cited by 124 · see citing works
Favier, F. B., Costes, F., Defour, A., Bonnefoy, R., Lefai, E., Baugé, S., Peinnequin, A., Benoit, H., & Freyssenet, D. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00550.2009 · Cited by 127 · see citing works
mTOR Signaling in Parkinson’s Disease
Lan, A., Chen, J., Zhao, Y., Chai, Z., & Hu, Y. (2016) · NeuroMolecular Medicine · doi:10.1007/s12017-016-8417-7 · Cited by 115 · see citing works
The Relevance of Insulin Action in the Dopaminergic System
Fiory, F., Perruolo, G., Cimmino, I., Cabaro, S., Pignalosa, F. C., Miele, C., Bèguinot, F., Formisano, P., & Oriente, F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00868 · Cited by 114 · see citing works
Therapeutic Effects of Rapamycin on MPTP-Induced Parkinsonism in Mice
Liu, K., Shi, N., Sun, Y., Zhang, T., & Sun, X. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0909-8 · Cited by 114 · see citing works
Zhou, Q., Liu, C., Liu, W., Zhang, H., Zhang, R., Liu, J., Zhang, J., Xu, C., Liu, L., Huang, S., et al. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu211 · Cited by 104 · see citing works
Multifaceted deaths orchestrated by mitochondria in neurones
Nagley, P., Higgins, G. C., Atkin, J. D., & Beart, P. M. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.09.004 · Cited by 103 · see citing works
Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases
Xiang, Y., Song, X., & Long, D. (2024) · Archives of Toxicology · doi:10.1007/s00204-023-03660-8 · Cited by 109 · see citing works
Polman, J. A. E., Hunter, R. G., Speksnijder, N., van den Oever, J. M. E., Korobko, O. B., McEwen, B. S., de Kloet, E. R., & Datson, N. A. (2012) · Endocrinology · doi:10.1210/en.2012-1255 · Cited by 100 · see citing works
Neuroprotection by Paeoniflorin in the MPTP mouse model of Parkinson's disease
Zheng, M., Liu, C., Fan, Y., Yan, P., Shi, D., & Zhang, Y. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.009 · Cited by 100 · see citing works
Hexokinase activity is required for recruitment of parkin to depolarized mitochondria
McCoy, M. K., Kaganovich, A., Rudenko, I. N., Ding, J., & Cookson, M. R. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt407 · Cited by 97 · see citing works
Emerging therapies for Parkinson's disease: From bench to bedside
Tarazi, F. I., Sahli, Z. T., Wolny, M., & Mousa, S. A. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.05.010 · Cited by 96 · see citing works
Jadiya, P., Garbincius, J. F., & Elrod, J. W. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01224-4 · Cited by 94 · see citing works
Molecular changes in the postmortem parkinsonian brain
Toulorge, D., Schapira, A. H. V., & Hajj, R. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13696 · Cited by 92 · see citing works
Millan, M. J. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.06.002 · Cited by 91 · see citing works
Luo, S., Kang, S. S., Wang, Z.-H., Liu, X., Day, J. X., Wu, Z., Peng, J., Xiang, D., Springer, W., & Ye, K. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0625-19.2019 · Cited by 83 · see citing works
Diabetes, a Contemporary Risk for Parkinson’s Disease: Epidemiological and Cellular Evidences
Sergi, D., Renaud, J., Simola, N., & Martinoli, M. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00302 · Cited by 85 · see citing works
Effects of DDIT4 in Methamphetamine-Induced Autophagy and Apoptosis in Dopaminergic Neurons
Li, B., Chen, R., Chen, L., Qiu, P., Ai, X., Huang, E., Huang, W., Chen, C., Liu, C., Lin, Z., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9637-9 · Cited by 86 · see citing works
Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
Dzamko, N. L., Zhou, J., Huang, Y. M., & Halliday, G. M. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00057 · Cited by 82 · see citing works
Al-Sweidi, S., Sánchez, M. G., Bourque, M., Morissette, M., Dluzen, D. E., & Paolo, T. D. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02193.x · Cited by 82 · see citing works
Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?
Bu, Z., Yu, H., Wang, J., He, X., Cui, Y., Feng, J., & Feng, J. (2021) · ASN NEURO · doi:10.1177/17590914211037505 · Cited by 87 · see citing works
Gu, Y., Kaufman, J. L., Bernal, L., Torre, C., Matulis, S. M., Harvey, R. D., Chen, J., Sun, S., Boise, L., & Lonial, S. (2014) · Blood · doi:10.1182/blood-2013-08-521914 · Cited by 81 · see citing works
The role of glycogen synthase kinase 3 beta in neurodegenerative diseases
Yu, H., Xiong, M., & Zhang, Z. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1209703 · Cited by 79 · see citing works
A neuroprotective role for angiogenin in models of Parkinson’s disease
Steidinger, T. U., Standaert, D. G., & Yacoubian, T. A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07112.x · Cited by 76 · see citing works
Ferroptosis: A potential therapeutic target for neurodegenerative diseases
Vitalakumar, D., Sharma, A., & Flora, S. J. S. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22830 · Cited by 73 · see citing works
Is REDD1 a metabolic double agent? Lessons from physiology and pathology
Britto, F. A., Dumas, K., Giorgetti‐Peraldi, S., Ollendorff, V., & Favier, F. B. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00340.2020 · Cited by 70 · see citing works
Fang, X., Zhou, X., Miao, Y., Han, Y., Wei, J., & Chen, T. (2020) · AMB Express · doi:10.1186/s13568-020-01014-6 · Cited by 70 · see citing works
Bourque, M., Dluzen, D. E., & Paolo, T. D. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.02.003 · Cited by 69 · see citing works
Iron Metabolism of the Skeletal Muscle and Neurodegeneration
Hałoń, M., Borkowska, A., Herman-Antosiewicz, A., & Antosiewicz, J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00165 · Cited by 69 · see citing works
Akt as a Victim, Villain and Potential Hero in Parkinson’s Disease Pathophysiology and Treatment
Greene, L. A., Levy, O., & Malagelada, C. (2011) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-011-9671-8 · Cited by 68 · see citing works
Self-citationImplication of REDD1 in the activation of inflammatory pathways
Pastor, F., Dumas, K., Barthelemy, M., Regazzetti, C., Druelle, N., Peraldi, P., Cormont, M., Tanti, J., & Giorgetti-Peraldi, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-07182-z · Cited by 55 · see citing works
RTP801/REDD1 Regulates the Timing of Cortical Neurogenesis and Neuron Migration
Malagelada, C., López-Toledano, M. A., Willett, R. T., Jin, Z. H., Shelanski, M. L., & Greene, L. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4011-10.2011 · Cited by 59 · see citing works
Self-citation(2020) · International Review of Neurobiology · doi:10.1016/bs.irn.2020.02.010 · Cited by 58 · see citing works
Unraveling Parkinson’s Disease Neurodegeneration: Does Aging Hold the Clues?
Coleman, C., & Martin, I. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223363 · Cited by 59 · see citing works
The stress-responsive protein REDD1 and its pathophysiological functions
Kim, J., Kwon, Y., & Kim, Y. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01056-3 · Cited by 59 · see citing works
Canal, M., Romaní-Aumedes, J., Martín‐Flores, N., Pérez-Fernández, V., & Malagelada, C. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00313 · Cited by 57 · see citing works
Self-citationOxidative Modification and Its Implications for the Neurodegeneration of Parkinson’s Disease
Zhao, J., Yu, S., Zheng, Y., Yang, H., & Zhang, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9743-3 · Cited by 55 · see citing works
Lin, C., Lin, H.-I., Chen, M., Lai, T.-T., Cao, L., Farrer, M. J., Wu, R., & Chien, C. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw068 · Cited by 54 · see citing works
El-Sherbeeny, N. A., Soliman, N., Youssef, A. M., El‐Fadeal, N. M. A., El-Abaseri, T. B., Hashish, A. A., Abdelbasset, W. K., Batiha, G. E., & Zaitone, S. A. (2020) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2020.111344 · Cited by 53 · see citing works
Ahmad, F., Nidadavolu, P., Durgadoss, L., & Ravindranath, V. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.06.004 · Cited by 53 · see citing works
Thomas, M. G., Saldanha, M., Mistry, R. J., Dexter, D. T., Ramsden, D. B., & Parsons, R. B. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.200 · Cited by 53 · see citing works
Rho Kinase and Dopaminergic Degeneration: A Promising Therapeutic Target for Parkinson’s Disease
Labandeira-Garcia, J. L., Rodríguez-Perez, A. I., Villar-Cheda, B., Borrajo, A., Dominguez-Meijide, A., & Guerra, M. J. (2015) · The Neuroscientist · doi:10.1177/1073858414554954 · Cited by 54 · see citing works
The role of NURR1 in metabolic abnormalities of Parkinson’s disease
Al‐Nusaif, M., Yang, Y., Li, S., Cheng, C., & Le, W. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00544-w · Cited by 52 · see citing works
Farid, H. A., Sayed, R. H., El-Shamarka, M. E.-S., Abdel‐Salam, O. M. E., & Sayed, N. S. E. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01305-x · Cited by 52 · see citing works
Martinez, T. N., Chen, X., Bandyopadhyay, S., Merrill, A. H., & Tansey, M. G. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-45 · Cited by 52 · see citing works
Ras Homolog Enriched in Brain (Rheb) Enhances Apoptotic Signaling*
Karassek, S., Berghaus, C., Schwarten, M., Goemans, C. G., Ohse, N., Kock, G., Jockers, K. F. G., Neumann, S., Gottfried, S., Herrmann, C., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.095968 · Cited by 51 · see citing works
PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and protection against apoptosis
Akundi, R. S., Zhi, L., & Büeler, H. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.08.034 · Cited by 50 · see citing works
Parkin loss of function contributes to RTP801 elevation and neurodegeneration in Parkinson’s disease
Romaní-Aumedes, J., Canal, M., Martín‐Flores, N., Sun, X., Pérez-Fernández, V., Wewering, S., Fernández‐Santiago, R., Ezquerra, M., Pont‐Sunyer, C., Lafuente, A., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.333 · Cited by 50 · see citing works
Self-citationRegulation of mRNA Translation as a Conserved Mechanism of Longevity Control
Mehta, R., Chandler-Brown, D., Ramos, F. J., Shamieh, L. S., & Kaeberlein, M. (2010) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4419-7002-2_2 · Cited by 44 · see citing works
Hacıoğlu, G., Seval, Y., Tanrιöver, G., Özsoy, Ö., Saka, E., Balkan, S., & Ağar, A. (2012) · Folia Histochemica et Cytobiologica · doi:10.5603/fhc.2012.0032 · Cited by 48 · see citing works
MiR-133b ameliorates axon degeneration induced by MPP+ via targeting RhoA
Niu, M., Xu, R., Wang, J., Hou, B., & Xie, A. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.03.042 · Cited by 49 · see citing works
Sekar, S., & Taghibiglou, C. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.12.049 · Cited by 49 · see citing works
Durgadoss, L., Nidadavolu, P., Valli, R. K., Saeed, U., Mishra, M., Seth, P., & Ravindranath, V. (2011) · The FASEB Journal · doi:10.1096/fj.11-194100 · Cited by 48 · see citing works
Striatal Akt/GSK3 signaling pathway in the development of L-Dopa-induced dyskinesias in MPTP monkeys
Morissette, M., Samadi, P., Tahar, A. H., Bélanger, N., & Di Paolo, T. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.12.011 · Cited by 47 · see citing works
Feedback Control of p53 Translation by REDD1 and mTORC1 Limits the p53-Dependent DNA Damage Response
Vadysirisack, D. D., Baenke, F., Ory, B., Lei, K., & Ellisen, L. W. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05541-11 · Cited by 48 · see citing works
Zhang, W., He, H., Song, H., Zhao, J., Li, T., Wu, L., Zhang, X., & Chen, J. (2016) · Parkinson s Disease · doi:10.1155/2016/9450137 · Cited by 46 · see citing works
RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease
Pérez‐Sisqués, L., Sancho‐Balsells, A., Solana‐Balaguer, J., Campoy‐Campos, G., Vives-Isern, M., Soler-Palazón, F., Anglada‐Huguet, M., López-Toledano, M. A., Mandelkow, E., Alberch, J., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03899-y · Cited by 44 · see citing works
Self-citationBao, X.-Q., Kong, X., Qian, C., & Zhang, D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.11.036 · Cited by 45 · see citing works
Neuroactive gonadal drugs for neuroprotection in male and female models of Parkinson's disease
Litim, N., Morissette, M., & Paolo, T. D. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.09.024 · Cited by 45 · see citing works
Furlong, R. M., Lindsay, A. J., Anderson, K. E., Hawkins, P. T., Sullivan, A. M., & O’Neill, C. (2019) · Journal of Cell Science · doi:10.1242/jcs.233221 · Cited by 44 · see citing works
Neuroprotection by tetrahydroxystilbene glucoside in the MPTP mouse model of Parkinson's disease
Zhang, L., Huang, L., Chen, L.-W., Hao, D., & Chen, J. (2013) · Toxicology Letters · doi:10.1016/j.toxlet.2013.07.020 · Cited by 42 · see citing works
Muroyama, A., Fujita, A., Lv, C., Kobayashi, S., Fukuyama, Y., & Mitsumoto, Y. (2012) · Parkinson s Disease · doi:10.1155/2012/985157 · Cited by 42 · see citing works
Huang, C.-F., Liu, S., Su, C., Fang, K., Yen, C., Yang, C., Tang, F., Liu, J., Wu, C.-C., Lee, K.-I., et al. (2021) · Toxicology · doi:10.1016/j.tox.2021.152764 · Cited by 41 · see citing works
Fu, S.-C., Lin, J.-W., Liu, J., Liu, S., Fang, K., Su, C., Hsu, R., Wu, C.-C., Huang, C.-F., Lee, K.-I., et al. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.05.008 · Cited by 39 · see citing works
Coelho, B. P., Gaelzer, M. M., Petry, F. D. S., Hoppe, J. B., Trindade, V. M. T., Salbego, C. G., & Guma, F. T. C. R. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.02.005 · Cited by 38 · see citing works
- Authors
- Malagelada, C., Jin, Z. H., & Greene, L. A.
- Affiliations
- Columbia University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-12-31
- Volume
- 28
- Issue
- 53
- Pages
- 14363-14371
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3865436
- OpenAlex
- W2084140068
- Cited by
- 228
- References
- 50
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 15 · 2021: 20 · 2020: 13 · 2019: 17 · 2018: 10 · 2017: 9 · 2016: 19 · 2015: 11 · 2014: 15 · 2013: 13 · 2012: 19
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Parkinson's Disease Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (P50NS038370)
- 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 › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- RTP801, Parkinson's disease, dopaminergic neuron death, Akt phosphorylation, mTOR signaling, 6-hydroxydopamine, neurodegeneration, stress response, Akt/mTOR signaling
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Cells, Cultured, Gene Expression Regulation, Humans, Melanins, Neurons, Parkinson Disease, Phosphorylation, Serine, Substantia Nigra, Sympatholytics, Threonine, Time Factors, Transcription Factors, Transfection, Oxidopamine, Cell Death, Superior Cervical Ganglion, Green Fluorescent Proteins, Oncogene Protein v-akt, Rats
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