JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Formation of dopamine-mediated alpha-synuclein-soluble oligomers requires methionine oxidation.

alpha-Synuclein is the major component of the intracellular Lewy body inclusions present in Parkinson disease (PD) neurons. PD involves the loss of dopaminergic neurons in the substantia nigra and the subsequent depletion of dopamine (DA) in the striatum. DA can inhibit alpha-synuclein fibrillization in vitro and promote alpha-synuclein aggregation into soluble oligomers. We have studied the mechanism by which DA mediates alpha-synuclein aggregation into soluble oligomers. Reacting alpha-synuclein with DA increased the mass of alpha-synuclein by 64 Da. NMR showed that all four methionine residues were oxidized by DA, consistent with the addition of 64 Da. Substituting all four methionines to alanine significantly reduced the formation of DA-mediated soluble oligomers. The (125)YEMPS(129) motif in alpha-synuclein can modulate DA inhibition of alpha-synuclein fibrillization. However, alpha-synuclein ending before the (125)YEMPS(129) motif (residues 1-124) could still form soluble oligomers. The addition of exogenous synthetic YEMPS peptide inhibited the formation of soluble oligomers and resulted in the YEMPS peptide being oxidized. Therefore, the (125)YEMPS(129) acts as an antioxidant rather than interacting directly with DA. Our study defines methionine oxidation as the dominant mechanism by which DA generates soluble alpha-synuclein oligomers and highlights the potential role for oxidative stress in modulating alpha-synuclein aggregation.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app