| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Ren, Jing Wu, Chao Zeng, Mengxia Qu, Mingqin Gao, Ge Chen, Ning Yue, Jingjing Jiang, Yuwen Zhao, Tongfei Xiang, Na Meng, Fangang Lu, Ling-ling |
| Abstract | To investigate physiological function of α-synuclein is important for understanding its pathophysiological mechanism in synucleinopathies including Parkinson’s disease. Employing knockout mice, we found that Snac/α-synuclein deletion induced aberrant projection of olfactory sensory neurons and hyposmia. We identified 9 axon guidance associated differentially expressed proteins using iTRAQ based Liquid Chromatograph Mass Spectrometer. NCK2 is most significantly down-regulated protein among them. We further found that either α-synuclein deletion or NCK2 deficiency induced Eph A4 inactivation. Re-expressing Snac/α-synuclein in its knockout neurons reversed the down-regulation of NCK2, as well as the inactivation of EphA4. Overexpression of Snac/α-synuclein in α-synuclein deleted mice reversed the down-regulation of NCK2 and pEphA4, and improved the olfactory impairment of mice. Correlation analysis showed that there is a significant correlation between the protein level of α-synuclein, NCK2, and pEphA4, respectively. Nonetheless, immunoprecipitation analysis showed that NCK2 was associated with both EphA4 and Rho A, suggesting that NCK2 as a scaffolding protein to modulate Eph A4/Rho A pathway. Moreover, Rho A activity was significantly lower in α-synuclein deficient mice. Thus, α-synuclein regulates olfactory neurons projection through NCK2 dependent EphA4/Rho A pathway. Malfunction of α-synuclein because of deletion may cause aberrant olfactory neurons projection. This extended our knowledge of α-synuclein functions, which may explain why olfaction is usually impaired in some synucleinopathies. |
| Related Links | https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-024-01313-6.pdf |
| Ending Page | 17 |
| Page Count | 17 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20453701 |
| DOI | 10.1186/s13578-024-01313-6 |
| Journal | Cell & Bioscience |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-11-14 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Microbiology Stem Cells Neurobiology Proteomics Parkinson’s disease α-synuclein Ephs NCK2 Synucleinopathies |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 7/2023 |
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