Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
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Gege Yu
Abstract
Extensive studies have reported that interaction of α-synuclein amyloid species with neurons is a crucial mechanistic characteristic of Parkinson’s disease (PD) and small molecules can downregulate the neurotoxic effects induced by protein aggregation. However, the exact mechanism(s) of these neuroprotective effects by small molecules remain widely unknown. In the present study, α-synuclein samples in the amyloidogenic condition were aged for 120 h with or without different concentrations of mitoquinone (MitoQ) as a quinone derivative compound and the amyloid characteristics and the relevant neurotoxicity were evaluated by Thioflavin T (ThT)/Nile red fluorescence, Congo red absorption, circular dichroism (CD), transmission electron microscopy (TEM), cell viability, lactate dehydrogenase (LDH), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), and caspase-9/-3 activity assays. Results clearly showed the capacity of MitoQ on the inhibition of the formation of α-synuclein fibrillation products through modulation of the aggregation pathway by an effect on the kinetic parameters. Also, it was shown that α-synuclein samples aged for 120 h with MitoQ trigger less neurotoxic effects against SH-SY5Y cells than α-synuclein amyloid alone. Indeed, co-incubation of α-synuclein with MitoQ reduced the membrane leakage, oxidative and nitro-oxidative stress, modifications of macromolecules, and apoptosis.
Acknowledgments
We thank our colleagues for many scientific discussions and support of the last years.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest statement: The authors declare that there is no conflict of interests associated with this work.
References
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© 2021 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Research Articles
- Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
- Effect of myeloperoxidase oxidation and N-homocysteinylation of high-density lipoprotein on endothelial repair function
- High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis
- Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells
- Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
- M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
- Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches
- Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells
Artikel in diesem Heft
- Frontmatter
- Research Articles
- Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
- Effect of myeloperoxidase oxidation and N-homocysteinylation of high-density lipoprotein on endothelial repair function
- High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis
- Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells
- Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
- M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
- Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches
- Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells
