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alpha-Synuclein is phosphorylated in synucleinopathy lesions
Hideo Fujiwara1, Masato Hasegawa, Naoshi Dohmae
1Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature Cell Biology
|January 29, 2002
Summary
Phosphorylation of alpha-synuclein at Ser 129 is identified in synucleinopathy lesions, promoting fibril formation. This finding highlights the role of protein phosphorylation in neurodegenerative disease pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Synucleinopathies, including Parkinson's disease (PD), are characterized by alpha-synuclein aggregation.
- Genetic studies implicate alpha-synuclein in PD pathogenesis.
- Specific post-translational modifications driving alpha-synuclein aggregation remain unidentified.
Purpose of the Study:
- To identify specific post-translational modifications of alpha-synuclein in synucleinopathy lesions.
- To investigate the role of alpha-synuclein phosphorylation in fibril formation and disease pathogenesis.
Main Methods:
- Mass spectrometry analysis of brain tissue.
- Utilized an antibody specific for phospho-Ser 129 alpha-synuclein.
- In vitro studies on alpha-synuclein fibril formation.
Main Results:
- Selective and extensive phosphorylation of alpha-synuclein at Ser 129 was detected in synucleinopathy lesions.
- Phosphorylation at Ser 129 was shown to promote alpha-synuclein fibril formation in vitro.
Conclusions:
- Phosphorylation of alpha-synuclein at Ser 129 is a key modification in synucleinopathy pathogenesis.
- This modification promotes the aggregation of alpha-synuclein, contributing to neurodegeneration.
- Highlights the critical role of protein phosphorylation in neurodegenerative disorders.