We have located links that may give you full text access.
4,4'-Dimethoxychalcone regulates redox homeostasis by targeting riboflavin metabolism in Parkinson's disease therapy.
Free Radical Biology & Medicine 2021 July 29
Oxidative stress damage plays a pivotal role in Parkinson's disease (PD) pathogenesis. Previously, we developed a blood brain barrier-penetrating peptide-based "Trojan Horse" strategy to deliver 4,4'-dimethoxychalcone (DMC) for PD therapy and revealed neuroprotective properties of DMC in a PD model; however, the underlying mechanisms remained unclear. Here, we report that DMC attenuated motor impairment, degeneration of DA neurons and α-synuclein aggregation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and exogenous human α-synuclein-induced PD mouse models. Mechanistically, DMC increased the expression of two critical intermediates in riboflavin metabolism: riboflavin kinase (RFK) and its metabolic product, flavin mononucleotide (FMN). We provide the first direct evidence that FMN ameliorated oxidative stress damage and dopaminergic neuron degeneration both in vitro and in vivo and that riboflavin metabolism was required for DMC-mediated neuroprotection. DMC-induced restoration of redox homeostasis was mediated via the activation of protein kinase Cθ (PKCθ) signaling. Together, our findings reveal that DMC may serve as a novel antioxidant in PD intervention and also define a novel mechanism that underlies its therapeutic activity.
Full text links
Related Resources
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
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