PMID- 34653323
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220531
IS  - 1437-4315 (Electronic)
IS  - 1431-6730 (Linking)
VI  - 403
IP  - 3
DP  - 2022 Feb 23
TI  - Inhibitory effect of mitoquinone against the alpha-synuclein fibrillation and 
      relevant neurotoxicity: possible role in inhibition of Parkinson's disease.
PG  - 253-263
LID - 10.1515/hsz-2021-0312 [doi]
AB  - Extensive studies have reported that interaction of alpha-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, alpha-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 alpha-synuclein fibrillation products through modulation of the 
      aggregation pathway by an effect on the kinetic parameters. Also, it was shown 
      that alpha-synuclein samples aged for 120 h with MitoQ trigger less neurotoxic 
      effects against SH-SY5Y cells than alpha-synuclein amyloid alone. Indeed, 
      co-incubation of alpha-synuclein with MitoQ reduced the membrane leakage, oxidative 
      and nitro-oxidative stress, modifications of macromolecules, and apoptosis.
CI  - (c) 2021 Walter de Gruyter GmbH, Berlin/Boston.
FAU - Yu, Gege
AU  - Yu G
AD  - Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou 
      University, Luoyang, 471009, China.
FAU - Wang, Yonghui
AU  - Wang Y
AD  - Department of Neurosurgery, Qingzhou Hospital Affiliated to Shandong First 
      Medical University, Weifang, Shandong, 262500, China.
AD  - Department of Neurosurgery, Qingzhou People's Hospital, Weifang, 262500, China.
FAU - Zhao, Jinhua
AU  - Zhao J
AD  - Department of Neurology, The First People's Hospital of Xianyang, Xianyang, 
      712000, China.
LA  - eng
PT  - Journal Article
DEP - 20211015
PL  - Germany
TA  - Biol Chem
JT  - Biological chemistry
JID - 9700112
RN  - 0 (Amyloid)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (alpha-Synuclein)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
SB  - IM
MH  - Amyloid/metabolism
MH  - Humans
MH  - Organophosphorus Compounds
MH  - *Parkinson Disease/drug therapy
MH  - Ubiquinone/analogs & derivatives
MH  - *alpha-Synuclein/metabolism
OTO - NOTNLM
OT  - amyloid
OT  - inhibition
OT  - mitoquinone
OT  - neurotoxicity
OT  - alpha-synuclein
EDAT- 2021/10/16 06:00
MHDA- 2022/05/03 06:00
CRDT- 2021/10/15 17:21
PHST- 2021/07/08 00:00 [received]
PHST- 2021/09/16 00:00 [accepted]
PHST- 2021/10/16 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2021/10/15 17:21 [entrez]
AID - hsz-2021-0312 [pii]
AID - 10.1515/hsz-2021-0312 [doi]
PST - epublish
SO  - Biol Chem. 2021 Oct 15;403(3):253-263. doi: 10.1515/hsz-2021-0312. Print 2022 Feb 
      23.