The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Specificity and Regulation of Casein Kinase-Mediated Phosphorylation of α-Synuclein
Open accessAbstract
alpha-Synuclein (alpha-syn) is the major component of pathologic inclusions that characterize neurodegenerative disorders such as Parkinson disease, dementia with Lewy body disease, and multiple system atrophy. The present study uses novel phospho-specific antibodies to assess the presence and regulation of phosphorylated Ser87 and Ser129 in alpha-syn in human brain samples and in a transgenic mouse model of alpha-synucleinopathies. By immunohistochemistry, alpha-syn phosphorylated at Ser129, but not at Ser87, was abundant in alpha-syn inclusions. Under normal conditions, Ser129 phosphorylation, but not Ser87 phosphorylation, was detected at low levels in the soluble biochemical fractions in human alpha-syn transgenic mice and stably transfected cultured cells. Therefore, a role for Ser87 phosphorylation in alpha-synucleinopathies is unlikely, and in vitro assays showed that phosphorylation at this site would inhibit polymerization. In vitro studies also indicated that hyperphosphorylation of Ser129 alpha-syn in pathologic inclusions may be due in part to the intrinsic properties of aggregated alpha-syn to act as substrates for kinases but not phosphatases. Further studies in transgenic mice and cultured cells suggest that cellular toxicity, including proteasomal dysfunction, increases casein kinase 2 activity, which results in elevated Ser129 alpha-syn phosphorylation. These data provide novel explanations for the presence of hyperphosphorylated Ser129 alpha-syn in pathologic inclusions.
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
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Hyperphosphorylation and insolubility of α‐synuclein in transgenic mouse oligodendrocytes
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Cited by
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Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons
Guo, J. L., Covell, D. J., Daniels, J. P., Iba, M., Stieber, A., Zhang, B., Riddle, D. M., Kwong, L. K., Xu, Y., Trojanowski, J. Q., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.057 · Cited by 680
Cell Biology and Pathophysiology of α-Synuclein
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Metadata
- Authors
- Waxman, E. A., & Giasson, B. I.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05
- Volume
- 67
- Issue
- 5
- Pages
- 402-416
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1991322550
- Cited by
- 209
- References
- 7
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Waxman, E. A., & Giasson, B. I. (2008). Specificity and Regulation of Casein Kinase-Mediated Phosphorylation of α-Synuclein. Journal of Neuropathology & Experimental Neurology. https://doi.org/10.1097/nen.0b013e3186fc995
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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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