The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Accumulation of Toxic α-Synuclein Oligomer within Endoplasmic Reticulum Occurs in α-Synucleinopathy In Vivo
Open accessAbstract
In Parkinson's disease (PD) and other α-synucleinopathies, prefibrillar α-synuclein (αS) oligomer is implicated in the pathogenesis. However, toxic αS oligomers observed using in vitro systems are not generally seen to be associated with α-synucleinopathy in vivo. Thus, the pathologic significance of αS oligomers to αS neurotoxicity is unknown. Herein, we show that, αS that accumulate within endoplasmic reticulum (ER)/microsome forms toxic oligomers in mouse and human brain with the α-synucleinopathy. In the mouse model of α-synucleinopathy, αS oligomers initially form before the onset of disease and continue to accumulate with the disease progression. Significantly, treatment of αS transgenic mice with Salubrinal, an anti-ER stress compound that delays the onset of disease, reduces ER accumulation of αS oligomers. These results indicate that αS oligomers with toxic conformation accumulate in ER, and αS oligomer-dependent ER stress is pathologically relevant for PD.
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Cites
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
α-Synuclein impairs macroautophagy: implications for Parkinson’s disease
Winslow, A. R., Chen, C.-W., Corrochano, S., Acevedo-Arozena, A., Gordon, D. E., Peden, A. A., Lichtenberg, M., Menzies, F. M., Ravikumar, B., Imarisio, S., et al. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201003122 · Cited by 825 · cited 1×
“Toxic S oligomers in ER/Ms in A53T S Tg mouse model of -synucleinopathy Studies indicate that S can functionally impact multiple organelles (Gosavi et al., 2002; Smith et al., 2005; Cooper et al., 2006; Martinez-Vicente et al., 2008; Winslow et al., 2010).”
BackgroundMartin, L. J., Pan, Y., Price, A. C., Sterling, W., Copeland, N. G., Jenkins, N. A., Price, D. L., & Lee, M. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4308-05.2006 · Cited by 684
Self-citation
Cited by
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Hetz, C., & Mollereau, B. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3689 · Cited by 684
Phase separation and neurodegenerative diseases: a disturbance in the force
Zbinden, A., Pérez-Berlanga, M., De Rossi, P., & Polymenidou, M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.014 · Cited by 500
Alpha-Synuclein Oligomers—Neurotoxic Molecules in Parkinson's Disease and Other Lewy Body Disorders
Ingelsson, M. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00408 · Cited by 344
The Role of α-Synuclein Oligomers in Parkinson’s Disease
Du, X.-Y., Xie, X.-X., & Liu, R.-T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228645 · Cited by 234
Metadata
- Authors
- Colla, E., Jensen, P. H., Pletnikova, O., Troncoso, J. C., Glabe, C., & Lee, M. K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-03-07
- Volume
- 32
- Issue
- 10
- Pages
- 3301-3305
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1992241406
- Cited by
- 323
- References
- 3
- FWCI
- 14.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Colla, E., Jensen, P. H., Pletnikova, O., Troncoso, J. C., Glabe, C., & Lee, M. K. (2012). Accumulation of Toxic α-Synuclein Oligomer within Endoplasmic Reticulum Occurs in α-Synucleinopathy In Vivo. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.5368-11.2012
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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