Background: Alzheimer’s disease (AD) is the most frequent cause of dementia among the elderly. The accumulation of amyloid beta (Aβ) and its downstream pathological events such as oxidative stress play central roles in AD. Recent studies revealed that Aβ oligomer (AβO)-induced strong neurotoxicity in SH-SY5Y cells via the induction of oxidative stress. Objective: In the present study, we investigated the effect of two antioxidants, Tocovid and Twendee-X, on AβO-induced SH-SY5Y cell damage. Methods: AβOs (2.5 μM) were applied to induce cellular damage in the SH-SY5Y cell line. Cell viability following AβO toxicity, Tau protein phosphorylation, cell morphology, and intracellular reactive oxygen species were assayed with or without different concentrations of Tocovid or Twendee-X. Results: Tocovid (60 μg/mL) and Twendee-X (150 μg/mL) significantly recovered cell viability from AβO toxicity (**p < 0.01, vs. control), attenuated Tau protein phosphorylation (**p < 0.01, vs. AβOs), improved cell morphology (**p < 0.01, vs. AβOs), and suppressed intracellular ROS (**p < 0.01, vs. AβOs) in SH-SY5Y cells. Conclusion: These findings suggest the neuroprotective and therapeutic potential of Tocovid and Twendee-X for AD treatment.

1.
Briggs
R
,
Kennelly
SP
,
O’Neill
D
.
Drug treatments in Alzheimer’s disease
.
Clin Med
.
2016 Jun
;
16
(
3
):
247
53
. .
2.
Hishikawa
N
,
Fukui
Y
,
Sato
K
,
Kono
S
,
Yamashita
T
,
Ohta
Y
,
Characteristic features of cognitive, affective and daily living functions of late-elderly dementia
.
Geriatr Gerontol Int
.
2016 Apr
;
16
(
4
):
458
65
.
3.
Jiao
SS
,
Yao
XQ
,
Liu
YH
,
Wang
QH
,
Zeng
F
,
Lu
JJ
,
Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits
.
Proc Natl Acad Sci USA
.
2015 Apr
;
112
(
16
):
5225
30
.
4.
Cheignon
C
,
Tomas
M
,
Bonnefont-Rousselot
D
,
Faller
P
,
Hureau
C
,
Collin
F
.
Oxidative stress and the amyloid beta peptide in Alzheimer’s disease
.
Redox Biol
.
2018 Apr
;
14
:
450
64
. .
5.
Zhang
L
,
Guo
Y
,
Wang
H
,
Zhao
LL
,
Ma
ZL
,
Li
T
,
Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway
.
Life Sci
.
2019 Mar 15
;
221
:
259
66
.
6.
De Medeiros
LM
,
De Bastiani
MA
,
Rico
EP
,
Schonhofen
P
,
Pfaffenseller
B
,
Wollenhaupt-Aguiar
B
,
Cholinergic differentiation of human neuroblastoma SH-SY5Y cell line and its potential use as an in vitro model for Alzheimer’s disease studies
.
Mol Neurobiol
.
2019 Nov
;
56
(
11
):
7355
67
.
7.
Reiss
AB
,
Arain
HA
,
Stecker
MM
,
Siegart
NM
,
Kasselman
LJ
.
Amyloid toxicity in Alzheimer’s disease
.
Rev Neurosci
.
2018 Aug
;
29
(
6
):
613
27
. .
8.
Yasumoto
T
,
Takamura
Y
,
Tsuji
M
,
Watanabe-Nakayama
T
,
Imamura
K
,
Inoue
H
,
High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage
.
FASEB J
.
2019 Aug
;
33
(
8
):
9220
34
.
9.
Liu
Z
,
Li
T
,
Li
P
,
Wei
NN
,
Zhao
ZQ
,
Liang
HM
,
The ambiguous relationship of oxidative stress, Tau hyperphosphorylation, and autophagy dysfunction in Alzheimer’s disease
.
Oxid Med Cell Longev
.
2015
;
2015
:
352723
.
10.
Tönnies
E
,
Trushina
E
.
Oxidative stress, synaptic dysfunction, and Alzheimer’s disease
.
J Alzheimers Dis
.
2017
;
57
(
4
):
1105
21
.
11.
Kusaki
M
,
Ohta
Y
,
Inufusa
H
,
Yamashita
T
,
Morihara
R
,
Nakano
Y
,
Neuroprotective effects of a novel anti-oxidant mixture Twendee X in mouse stroke model
.
J Stroke Cerebrovasc Dis
.
2017 Jun
;
26
(
6
):
1191
6
.
12.
Shang
J
,
Yan
H
,
Jiao
Y
,
Ohta
Y
,
Liu
X
,
Li
XH
,
Therapeutic effects of pretreatment with Tocovid on oxidative stress in postischemic mice brain
.
J Stroke Cerebrovasc Dis
.
2018 Aug
;
27
(
8
):
2096
105
.
13.
Jiao
Y
,
Shang
J
,
Ohta
Y
,
Yan
HJ
,
Liu
X
,
Li
XH
,
Neuroprotective effects of Tocovid pretreatment in a mouse stroke model
.
J Stroke Cerebrovasc Dis
.
2018 Aug
;
27
(
8
):
2166
74
.
14.
Liu
X
,
Yamashita
T
,
Shang
J
,
Shi
XW
,
Morihara
R
,
Huang
Y
,
Twendee X ameliorates phosphorylated Tau, α-Synuclein and neurovascular dysfunction in Alzheimer’s disease transgenic mice with chronic cerebral hypoperfusion
.
J Stroke Cerebrovasc Dis
.
2019 Oct
;
28
(
10
):
104310
.
15.
Herzer
S
,
Meldner
S
,
Rehder
K
,
Gröne
HJ
,
Nordström
V
.
Lipid microdomain modification sustains neuronal viability in models of Alzheimer’s disease
.
Acta Neuropathol Commun
.
2016 Sep 17
;
4
(
1
):
103
. .
16.
Wen
J
,
Fang
F
,
Guo
SH
,
Zhang
Y
,
Peng
XL
,
Sun
WM
,
Amyloid β-derived diffusible ligands (ADDLs) induce abnormal autophagy associated with Aβ aggregation degree
.
J Mol Neurosci
.
2018 Feb
;
64
(
2
):
162
74
.
17.
Coullery
RP
,
Ferrari
ME
,
Rosso
SB
.
Neuronal development and axon growth are altered by glyphosate through a WNT non-canonical signaling pathway
.
Neurotoxicology
.
2016 Jan
;
52
:
150
61
. .
18.
Kamat
PK
,
Kalani
A
,
Rai
S
,
Swarnkar
S
,
Tota
S
,
Nath
C
,
Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease: understanding the therapeutics strategies
.
Mol Neurobiol
.
2016 Jan
;
53
(
1
):
648
61
.
19.
Martínez
MA
,
Rodríguez
JL
,
Lopez-Torres
B
,
Martínez
M
,
Martínez-Larrañaga
MR
,
Maximiliano
JE
,
Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways
.
Environ Int
.
2020 Feb
;
135
:
105414
.
20.
Feng
T
,
Yamashita
T
,
Tsunoda
K
,
Matsumoto
N
,
Tadokoro
K
,
Sasaki
R
,
In vitro free radical scavenging activities of dietary supplements by electron spin resonance
.
Brain Supplement
.
2020
;
2
:
1
12
.
21.
Abe
K
,
Kogure
K
,
Arai
H
,
Nakano
M
.
Ascorbate induced lipid peroxidation results in loss of receptor binding in tris, but not in phosphate, buffer. Implications for the involvement of metal ions
.
Biochem Int
.
1985 Sep
;
11
(
3
):
341
8
.
22.
Chakraborty
A
,
Jana
NR
.
Vitamin C-conjugated nanoparticle protects cells from oxidative stress at low doses but induces oxidative stress and cell death at high doses
.
ACS Appl Mater Interfaces
.
2017 Dec
;
9
(
48
):
41807
17
. .
23.
Kaźmierczak-Barańska
J
,
Boguszewska
K
,
Adamus-Grabicka
A
,
Karwowski
BT
.
Two faces of vitamin C-antioxidative and pro-oxidative agent
.
Nutrients
.
2020 May
;
12
(
5
):
1501
. .
24.
Neddens
J
,
Temmel
M
,
Flunkert
S
,
Kerschbaumer
B
,
Hoeller
C
,
Loeffler
T
,
Phosphorylation of different tau sites during progression of Alzheimer’s disease
.
Acta Neuropathol Commun
.
2018 Jun
;
6
(
1
):
52
.
25.
Barthélemy
NR
,
Bateman
RJ
,
Hirtz
C
,
Marin
P
,
Becher
F
,
Sato
C
,
Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer’s disease and PET amyloid-positive patient identification
.
Alzheimers Res Ther
.
2020 Mar
;
12
(
1
):
26
.
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