Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson's disease.

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.

• Authors: Gege Yu, Yonghui Wang, Jinhua Zhao
• Journal: Biological chemistry (Biol Chem) Vol. 403 Issue 3 Pg. 253-263 (02 23 2022) ISSN: 1437-4315 [Electronic] Germany
• PMID: 34653323 (Publication Type: Journal Article)
• Copyright: © 2021 Walter de Gruyter GmbH, Berlin/Boston.

Chemical References

• Amyloid
• Organophosphorus Compounds
• alpha-Synuclein
• Ubiquinone
• mitoquinone

Topics

• Amyloid (metabolism)
• Humans
• Organophosphorus Compounds
• Parkinson Disease (drug therapy)
• Ubiquinone (analogs & derivatives)
• alpha-Synuclein (metabolism)