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P75 Involved in the Ubiquitination of α-synuclein in Rotenone-based Parkinson’s Disease Models.
- Source :
-
Neuroscience . Sep2018, Vol. 388, p367-373. 7p. - Publication Year :
- 2018
-
Abstract
- Highlights • P75 regulated α-syn expression. • Dysregulation of siAH interacted with p75. • P75 controlled nuclear expression of p65. Abstract For Parkinson’s disease (PD), the regulatory mechanism of α-synuclein (α-syn) aggregation remains to be clarified. Ubiquitination modification is crucial for α-syn aggregation, with implications for Lewy body formation. Besides, ubiquitin ligase absentia homolog (siAH) is involved in the ubiquitination of α-syn. We investigated whether the p75 receptor can act as a potential regulator of α-syn accumulation through ubiquitination. Western blot, immunoprecipitation, gene transfection, and RNA interference technology were employed to detect the effect of p75 in in vivo and in vitro models. In a rotenone-based stereotactic (ST) infusion in vivo model of PD, p75 receptor and siAH expression was increased significantly compared with the control group. In cellular models of rotenone-mediated neurotoxicity, the interactions between p75 and siAH were revealed by immunoprecipitation; the colocalization of p75 with α-syn was observed in the cytoplasm; p75 promoted nuclear expression of NF-κB (p65), which might interact with the promoter of the siAH gene. Moreover, siRNA-mediated p75 depletion reduced the upregulation of α-syn and nuclear expression of p65 and protected against cell apoptosis induced by rotenone. Thus, aberrant expression of p75 may regulate the increased expression of α-syn, which is related to siAH-mediated ubiquitination and nuclear expression of p65. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 388
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 131608637
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2018.07.048