Neuropsychiatric Disease and Treatment,
Год журнала:
2023,
Номер
Volume 19, С. 2681 - 2696
Опубликована: Дек. 1, 2023
Background:
Wilson's
disease
(WD),
an
autosomal
recessive
genetic
disease,
is
characterized
by
copper
metabolism
disorder.
WD
patients
may
have
a
series
of
cognitive
deficits
in
terms
neurological
symptoms.
Ferroptosis
(FPT),
type
programmed
cell
death,
involved
the
pathological
progression
various
disorders,
and
silent
information
regulator
1
(SIRT1)
considered
to
be
key
factor
FPT.
Ferulic
acid
(FA)
traditional
Chinese
medicine
monomer,
with
remarkable
effect
clinical
treatment
impairment-related
disease.
However,
its
intrinsic
on
FPT
still
unclear.
This
study
aims
investigate
protective
FA
impairment
animal
models
WD,
whether
pharmacological
mechanism
related
SIRT1-mediated
signaling
pathway.
Methods:
Copper-loaded
rats
PC12
cells
were
used
as
dysfunction
vivo
vitro,
respectively.
Morris
Water
Maze
(MWM)
was
evaluate
spatial
exploration
memory
abilities
rats.
HE
staining
observe
neuronal
damage
CA1
region
rat
hippocampus.
Immunofluorescence
(IF)
detect
expression
GPX4
protein.
Transmission
electron
microscopy
(TEM)
ultrastructure
neurons.
The
levels
Fe2+,
MDA,
SOD,
GSH,
4HNE,
ROS
detected.
Western
blot
qRT-PCR
protein
mRNA
SIRT1,
Nrf2,
SCL7A11,
GPX4.
Results:
In
copper-loaded
model
rats,
MWM,
TEM,
IF
results
showed
that
could
promote
repair
learning
function,
improve
morphological
hippocampal
neurons,
maintain
mitochondria
integrity.
experiment,
MTT
method
increased
viability
copper-overloaded
models.
confirmed
significantly
proteins
addition,
reversed
oxidative
stress-related
indicators,
including
ROS.
Conclusion:
alleviates
injury
activating
FPT,
providing
valuable
candidate
for
monomer
therapeutics
impairment.
Keywords:
ferulic
acid,
impairment,
ferroptosis,
Redox Biology,
Год журнала:
2022,
Номер
57, С. 102511 - 102511
Опубликована: Окт. 14, 2022
Natural
antioxidants
represented
by
quercetin
have
been
documented
to
be
effective
against
atherosclerosis.
However,
the
related
mechanisms
remain
largely
unclear.
In
this
study,
we
identified
a
novel
anti-atherosclerotic
mechanism
of
inhibiting
macrophage
pyroptosis
activating
NRF2
through
binding
Arg483
site
KEAP1
competitively.
ApoE-/-
mice
fed
with
high
fat
diet,
administration
attenuated
atherosclerosis
progression
reducing
oxidative
stress
level
and
suppressing
pyroptosis.
At
cellular
level,
suppressed
THP-1
induced
ox-LDL,
demonstrated
NLRP3
inflammasome
activation
ROS
while
these
effects
were
reversed
specific
inhibitor
(ML385).
Mechanistically,
promoted
dissociate
from
KEAP1,
enhanced
nuclear
translocation
as
well
transcription
downstream
antioxidant
protein.
Molecular
docking
results
suggested
that
could
bind
at
Arg415
Arg483.
order
verify
sites,
mutated
Ser
(R415S
R483S)
was
transfected
into
macrophages,
anti-pyroptotic
effect
abrogated
mutation,
but
not
mutation.
Furthermore,
after
adeno
associated
viral
vector
(AAV)
AAV-KEAP1-R483S,
almost
abolished
in
mice.
These
findings
proved
quercetins
targeting
KEAP1/NRF2
interaction,
provided
reliable
data
on
underlying
natural
protect
Antioxidants,
Год журнала:
2024,
Номер
13(4), С. 395 - 395
Опубликована: Март 26, 2024
Central
neurological
disorders
are
significant
contributors
to
morbidity,
mortality,
and
long-term
disability
globally
in
modern
society.
These
encompass
neurodegenerative
diseases,
ischemic
brain
traumatic
injury,
epilepsy,
depression,
more.
The
involved
pathogenesis
is
notably
intricate
diverse.
Ferroptosis
neuroinflammation
play
pivotal
roles
elucidating
the
causes
of
cognitive
impairment
stemming
from
these
diseases.
Given
concurrent
occurrence
ferroptosis
due
metabolic
shifts
such
as
iron
ROS,
well
their
critical
central
nervous
disorders,
investigation
into
co-regulatory
mechanism
has
emerged
a
prominent
area
research.
This
paper
delves
mechanisms
along
with
interrelationship.
It
specifically
emphasizes
core
molecules
within
shared
pathways
governing
neuroinflammation,
including
SIRT1,
Nrf2,
NF-κB,
Cox-2,
iNOS/NO·,
how
different
immune
cells
structures
contribute
dysfunction
through
mechanisms.
Researchers’
findings
suggest
that
mutually
promote
each
other
may
represent
key
factors
progression
disorders.
A
deeper
comprehension
common
pathway
between
cellular
holds
promise
for
improving
symptoms
prognosis
related
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Янв. 2, 2025
Abstract
Rampant
phospholipid
peroxidation
initiated
by
iron
causes
ferroptosis
unless
this
is
restrained
cellular
defences.
Ferroptosis
increasingly
implicated
in
a
host
of
diseases,
and
unlike
other
cell
death
programs
the
physiological
initiation
conceived
to
occur
not
an
endogenous
executioner,
but
withdrawal
guardians
that
otherwise
constantly
oppose
induction.
Here,
we
profile
key
ferroptotic
defence
strategies
including
regulation,
modulation
enzymes
metabolite
systems:
glutathione
reductase
(GR),
suppressor
protein
1
(FSP1),
NAD(P)H
Quinone
Dehydrogenase
(NQO1),
Dihydrofolate
(DHFR),
retinal
reductases
dehydrogenases
(RDH)
thioredoxin
(TR).
A
common
thread
uniting
all
metabolites
combat
lipid
during
dependence
on
reductant,
nicotinamide
adenine
dinucleotide
phosphate
(NADPH).
We
will
outline
how
cells
control
central
carbon
metabolism
produce
NADPH
necessary
precursors
defend
against
ferroptosis.
Subsequently
discuss
evidence
for
dysregulation
different
disease
contexts
glucose-6-phosphate
dehydrogenase
deficiency,
cancer
neurodegeneration.
Finally,
several
anti-ferroptosis
therapeutic
spanning
use
radical
trapping
agents,
dependent
redox
support
highlight
current
landscape
clinical
trials
focusing
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
165, С. 115071 - 115071
Опубликована: Июнь 28, 2023
SIRT5
is
a
mitochondrial
NAD+
-dependent
lysine
deacylase.
Downregulation
of
has
been
linked
to
several
primary
cancers
and
DNA
damage.
In
clinical
therapy
for
non-small
cell
lung
cancer
(NSCLC),
the
Feiyiliu
Mixture
(FYLM)
an
experience
effective
Chinese
herb
prescription.
And
we
found
that
quercetin
important
ingredient
in
FYLM.
However,
whether
regulates
damage
repair
(DDR)
induces
apoptosis
through
NSCLC
remains
unknown.
The
present
study
revealed
directly
binds
inhibits
phosphorylation
PI3K/AKT
interaction
between
PI3K,
thus
inhibiting
process
homologous
recombination
(HR)
non-homologous
end-joining
(NHEJ)
NSCLC,
which
raise
mitotic
catastrophe
apoptosis.
Our
provided
novel
mechanism
action
treatment
NSCLC.
Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(19), С. 7427 - 7439
Опубликована: Май 3, 2023
Acrylamide
(ACR)
generated
in
carbohydrate-rich
foods
during
thermal
processing
has
been
demonstrated
to
exhibit
hepatotoxicity.
As
one
of
the
most
consumed
flavonoids
with
diet,
quercetin
(QCT)
possesses
ability
protect
against
ACR-induced
toxicity,
albeit
its
mechanism
is
unclear.
Herein,
we
discovered
that
QCT
alleviated
elevated
levels
reactive
oxygen
species
(ROS),
AST,
and
ALT
mice.
RNA-seq
analysis
revealed
reversed
ferroptosis
signaling
pathway
upregulated
by
ACR.
Subsequently,
experiments
indicated
inhibited
through
reduction
oxidative
stress.
With
autophagy
inhibitor
chloroquine,
further
confirmed
suppressed
inhibiting
stress-driven
autophagy.
Additionally,
specifically
reacted
autophagic
cargo
receptor
NCOA4,
blocked
degradation
iron
storage
protein
FTH1,
eventually
downregulated
intracellular
consequent
ferroptosis.
Collectively,
our
results
presented
a
unique
approach
alleviate
liver
injury
targeting
QCT.
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
72(22), С. 12340 - 12355
Опубликована: Май 22, 2024
Lipid
peroxidation
(LP)
leads
to
changes
in
the
fluidity
and
permeability
of
cell
membranes,
affecting
normal
cellular
function
potentially
triggering
apoptosis
or
necrosis.
This
process
is
closely
correlated
with
onset
many
diseases.
Evidence
suggests
that
phenolic
hydroxyl
groups
food-borne
plant
polyphenols
(FPPs)
make
them
effective
antioxidants
capable
preventing
diseases
triggered
by
membrane
LP.
Proper
dietary
intake
FPPs
can
attenuate
oxidative
stress,
especially
damage
phospholipids,
activating
Nrf2/GPx4
pathway.
Nuclear
factor
E2-related
2
(Nrf2)
an
stress
antagonist.
The
signaling
pathway
regulated
Nrf2
a
defense
transduction
organism
against
external
stimuli
such
as
reactive
oxygen
species
exogenous
chemicals.
Glutathione
peroxidase
4
(GPx4),
under
regulation
Nrf2,
only
enzyme
reduces
lipid
peroxides
specificity,
thus
playing
pivotal
role
regulating
ferroptosis
counteracting
stress.
study
explored
mechanism,
antioxidant
activity
FPPs,
mechanism
It
also
highlighted
bioprotective
properties
LP
its
associated
mechanisms,
including
(i)
activation
pathway,
GPx4
serving
central
target
protein,
(ii)
activities,
leading
reduction
production
ROS
other
peroxides,
(iii)
effects
on
downstream
phospholipid
structure.
In
conclusion,
play
crucial
natural
However,
further
in-depth
analysis
coregulation
multiple
pathways
required,
combined
these
mechanisms
need
evaluation
experimental
models.
Human
trials
could
provide
valuable
insights
into
new
directions
for
research
application.
