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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

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Waxman, Elisa A., Giasson, Benoit I.·2008·Journal of Neuropathology & Experimental Neurology

Abstract

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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Metadata

Authors
Waxman, E. A., & Giasson, B. I.
Venue
Journal of Neuropathology & Experimental Neurology
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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CoChat. (2026). Citation check: Specificity and Regulation of Casein Kinase-Mediated Phosphorylation of α-Synuclein. https://app.cochat.ai/papers/10.1097/nen.0b013e3186fc995
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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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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.