The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
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.
Overview
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
Verification
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?
In the citing paper
“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.
Citations
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
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
Greene, L., & Tischler, A. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.7.2424 · Cited by 5,566
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
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 3,051
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 3,014
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
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
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
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
Research works printed but not linked: 2
- 1997, Histol Histopathol, 12, 25
- 2006, Soc Neurosci Abstr, 32, 221
Cited by
Sorted by citations
Items 201–228 of 228
ROS and Redox Mechanism in Neurodegenerative Diseases
Zuo, L., Arballo, J., Liu, Z., & He, F. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11517-x · Cited by 2
Wang, Y., Gu, L., Yang, H., & Zhang, H. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.02.003 · Cited by 2
Role of IGF-1 in Neuroinflammation and Cogniton Deficits Induced by Sleep DeprivationPreprint
Wan, Y., Gao, W. Y., Zhou, K., Liu, X., Zheng, P., Xue, R., & Wu, W. (2021) · Research Square · doi:10.21203/rs.3.rs-680306/v1 · Cited by 2
Tiny Messengers, Huge Consequences: Extracellular Vesicles and mTOR Signaling in Neuroinflammation
Garcia‐Segura, P., Chicote‐González, A., Espasa‐Marco, A., Garcia‐Alcaraz, M., Mora‐Bernabé, L., Abelló‐Fernández, M., & Malagelada, C. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70256 · Cited by 2
Self-citationReudhabibadh, R., Champoochana, N., Kuedo, Z., Thammanichanon, P., Hutamekalin, P., & Binlateh, T. (2025) · Food and Chemical Toxicology · doi:10.1016/j.fct.2025.115821 · Cited by 1
Role of Impaired Insulin Signaling in the Pathogenesis of Dementia
Ahlawat, A., Walia, V., & Garg, M. (2022) · Springer eBooks · doi:10.1007/978-981-16-7606-2_3 · Cited by 2
Chen, M., He, X., Fan, Y., Lei, X., & Dong, Z. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09852-4 · Cited by 1
DDIT4 (DNA-damage-inducible transcript 4)
Vega-Rubín-de-Celis, S., & Brugarolas, J. (2013) · Atlas of Genetics and Cytogenetics in Oncology and Haematology · doi:10.4267/2042/50190 · Cited by 1
Aimé, P., Sun, X., & Greene, L. A. (2018) · InTech eBooks · doi:10.5772/intechopen.71811 · Cited by 1
Self-citationOverexpression of p58ipk protects neuroblastoma against paraquat-induced toxicity.
Li, F., Ge, B., & Damirin, A. (2017) · PubMed Central · Cited by 1
Serum IGF-I, Life Style, and Risk of Alzheimer’s disease
Piriz, J., Nishijima, T., Trejo, J. L., & Torres‐Alemán, I. (2010) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-04300-0_12
Determining the Role of Trib3 in Neuronal Apoptosis
Zareen, N. (2012) · doi:10.7916/d8tf04gw
Molecular basis of L-DOPA-induced dyskinesia : Studies on striatal signaling
Santini, E. (2009) · Figshare
Redox Signalling in Dopaminergic Cell Death and Survival
Ray, A., Verma, A., & Ravindranath, V. (2017) · Royal Society of Chemistry eBooks · doi:10.1039/9781782622888-00210
Şanlı, E., Yalçınkaya, N., & Tüzün, E. (2018) · Experimed · doi:10.26650/experimed.2018.0003
Peethambaran, B., Leonce, C., & Patel, A. (2021) · International Journal of Complementary & Alternative Medicine · doi:10.15406/ijcam.2021.14.00528
Blagojević, S., Jeremić, M., & Jovanović-Tucović, M. (2021) · Medicinski podmladak · doi:10.5937/mp72-33532
Solana‐Balaguer, J., Martín‐Flores, N., Garcia‐Segura, P., Campoy‐Campos, G., Pérez‐Sisqués, L., Chicote‐González, A., Fernández‐Irigoyen, J., Santamaría, E., Pérez‐Navarro, E., Alberch, J., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2736462/v1
Self-citationMetabolic regulatory proteins play an intermediate role in diabetes and Parkinson’s disease
Roy, R., Paul, S., & Chattopadhyay, K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33355-2.00038-4
Systems Biology of Aging: Opportunities for Parkinson’s Disease
Kriete, A. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3411-5_3
Champarini, L. G., Herrera, M. L., Cometto, M. J., Bartolozzi, R., Naranjo-Viteri, A. J., Crespo, R., Calfa, G. D., & Hereñú, C. B. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1781503
Decoding Parkinson’s disease: Insights from machine learning-based transcriptomic analysis
Aafrine, S., & Hossain, S. M. (2026) · Gene Reports · doi:10.1016/j.genrep.2026.102549
Sánchez-Thomas, R., Bautista-Perez, S. M., Santana-Martínez, R. A., Silva‐Islas, C. A., Figueroa, A., Barrera‐Oviedo, D., & Maldonado, P. D. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44173-8.00015-2
Fang, X., Wang, Y., Long, Z., Liao, B., Wang, B., Hong, D., Luo, J., & Chen, T. (2026) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2500237
Demmings, M. D., Kane, E. A., Tennyson, E. C., Hurley, K., Zhao, J., Cruickshanks, N. A., Ciz, V., Krupa, J. M., Pasternak, S., & Cregan, S. P. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117832 · Cited by 1
Xiao, L., Wu, Y., Huang, X., Deng, H., Wu, Y., Pan, W., Wang, W., & Wang, M. (2026) · Biology · doi:10.3390/biology15171503
Cabré, L. R. (2012) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Metadata
- 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 › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
