The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Proteolytic Cleavage of Extracellular Secreted α-Synuclein via Matrix Metalloproteinases
Open accessAbstract
Although alpha-synuclein is the main structural component of the insoluble filaments that form Lewy bodies in Parkinson disease (PD), its physiological function and exact role in neuronal death remain poorly understood. In the present study, we examined the possible functional relationship between alpha-synuclein and several forms of matrix metalloproteinases (MMPs) in the human dopaminergic neuroblastoma (SK-N-BE) cell line. When SK-N-BE cells were transiently transfected with alpha-synuclein, it was secreted into the extracellular culture media, concomitantly with a significant decrease in cell viability. Also the addition of nitric oxide-generating compounds to the cells caused the secreted alpha-synuclein to be digested, producing a small fragment whose size was similar to that of the fragment generated during the incubation of alpha-synuclein with various MMPs in vitro. Among several forms of MMPs, alpha-synuclein was cleaved most efficiently by MMP-3, and MALDI-TOF mass spectra analysis showed that alpha-synuclein is cleaved from its C-terminal end with at least four cleavage sites within the non-Abeta component of AD amyloid sequence. Compared with the intact form, the protein aggregation of alpha-synuclein was remarkably facilitated in the presence of the proteolytic fragments, and the fragment-induced aggregates showed more toxic effect on cell viability. Moreover, the levels of MMP-3 were also found to be increased significantly in the rat PD brain model produced by the cerebral injection of 6-hydroxydopamine into the substantia nigra. The present study suggests that the extracellularly secreted alpha-synuclein could be processed via the activation of MMP-3 in a selective manner.
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Cites
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death
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Phosphorylated α-Synuclein Is Ubiquitinated in α-Synucleinopathy Lesions
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Cited by
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115
“Using a similar model, Sung et al. (2005) demonstrated that secreted -synuclein from SK-N-BE cells reduces the viability of these cells and can be cleaved by matrix metalloproteases.”
BackgroundMatrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers
Rempe, R. G., Hartz, A. M., & Bauer, B. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16655551 · Cited by 721
Cell Biology and Pathophysiology of α-Synuclein
Burré, J., Sharma, M., & Südhof, T. C. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024091 · Cited by 579
Synuclein activates microglia in a model of Parkinson's disease
Su, X., Maguire-Zeiss, K. A., Giuliano, R., Prifti, L., Venkatesh, K., & Federoff, H. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.006 · Cited by 474
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-citation
Metadata
- Authors
- Sung, J. Y., Park, S. M., Lee, C.-H., Um, J. W., Lee, H. J., Kim, J., Oh, Y. J., Lee, S.-T., Paik, S. R., & Chung, K. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 280
- Issue
- 26
- Pages
- 25216-25224
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2123869107
- Cited by
- 238
- References
- 12
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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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.
