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RETRACTED: α‐Synuclein regulates neuronal survival via Bcl‐2 family expression and PI3/Akt kinase pathway
Abstract
α‐Synuclein (α‐SN) is a ubiquitous protein that is especially abundant in the brain and has been postulated to play a central role in the pathogenesis of Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders. However, little is known about the neuronal functions of α‐SN and the molecular and cellular mechanisms underlying neuronal loss. Here, we show that α‐SN plays dual roles of neuroprotection and neurotoxicity depending on its concentration or level of expression. At nanomolar concentrations, α‐SN protected neurons against serum deprivation, oxidative stress, and excitotoxicity through the PI3/Akt signaling pathway, and its protective effect was increased by Bcl‐2 overexpression. Conversely, at both low micromolar and overexpressed levels in the cell, α‐SN resulted in cytotoxicity. This might be related to decreased Bcl‐xL expression and increased bax expression, which is subsequently followed by cytochrome c release and caspase activation and also by microglia‐mediated inflammatory responses via the NFκB and mitogen‐activated protein kinase pathways.
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Cites
Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., Ryan, A., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)80886-7 · Cited by 1,722
Borghi, R., Marchese, R., Negro, A., Marinelli, L., Forloni, G., Zaccheo, D., Abbruzzese, G., & Tabaton, M. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01153-8 · Cited by 363
Cited by
The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
El-Agnaf, O. M. A., Salem, S. A., Paleologou, K. E., Cooper, L. J., Fullwood, N. J., Gibson, M. J., Curran, M. D., Court, J. A., Mann, D. M. A., Ikeda, S.-I., et al. (2003) · The FASEB Journal · doi:10.1096/fj.03-0098fje · Cited by 590
Assembly-dependent endocytosis and clearance of extracellular a-synuclein
Lee, H.-J., Suk, J.-E., Bae, E.-J., Lee, J.-H., Paik, S. R., & Lee, S.-J. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.017 · Cited by 470
Self-citationPart II: α-synuclein and its molecular pathophysiological role in neurodegenerative disease
Dev, K. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00140-0 · Cited by 263
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
Metadata
- Authors
- Seo, J., Rah, J., Choi, S. H., Shin, J. K., Min, K., Kim, H., Park, C. H., Kim, S., Kim, E., Lee, S., Lee, S., Won Suh, S., & Suh, Y.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2002-09-05
- Volume
- 16
- Issue
- 13
- Pages
- 1-20
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2140955387
- Cited by
- 208
- References
- 2
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- closed
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- CoChat. (2026). Citation check: RETRACTED: α‐Synuclein regulates neuronal survival via Bcl‐2 family expression and PI3/Akt kinase pathway. https://app.cochat.ai/papers/10.1096/fj.02-0041fje
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- Seo, J., Rah, J., Choi, S. H., Shin, J. K., Min, K., Kim, H., Park, C. H., Kim, S., Kim, E., Lee, S., Lee, S., Won Suh, S., & Suh, Y. (2002). RETRACTED: α‐Synuclein regulates neuronal survival via Bcl‐2 family expression and PI3/Akt kinase pathway. The FASEB Journal. https://doi.org/10.1096/fj.02-0041fje
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
