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Parkin suppresses wild-type alpha-synuclein-induced toxicity in SHSY-5Y cells
Yemisi Oluwatosin-Chigbu1, Alan Robbins, Clay W Scott
1Department of Molecular Science, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850-5437, USA.
Biochemical and Biophysical Research Communications
|September 10, 2003
Summary
Parkin protein protects against neuronal cell death caused by both mutant and wild-type alpha-synuclein (alphaS). This suggests parkin has a protective role in Parkinson's disease (PD) and related synucleopathies.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Parkinson's disease (PD) and synucleopathies involve neuronal cell death.
- Current theories suggest parkin and alpha-synuclein (alphaS) interact functionally.
- Parkin has been shown to suppress toxicity from mutant alphaS in neurons.
Purpose of the Study:
- To investigate if parkin also associates with and protects against wild-type (wt) alphaS.
- To explore the functional relationship between parkin and wt alphaS in neuronal cells.
Main Methods:
- Adenoviral infection to induce alphaS over-expression in SHSY-5Y cells.
- Assessing cellular toxicity by measuring ATP levels.
- Western blot analysis to detect alphaS-immunoreactive bands.
Main Results:
- Parkin suppressed toxicity induced by both mutant (A53T) and wt alphaS.
- Over-expression of parkin correlated with higher molecular weight alphaS bands.
- Evidence supports a protective role for parkin against alphaS-induced toxicity.
Conclusions:
- Parkin demonstrates a protective function against alphaS toxicity, including the wild-type form.
- These findings extend the known functional association between parkin and alphaS.
- Parkin may play a crucial role in mitigating neuronal loss in synucleinopathies.