Redox Biology,
Год журнала:
2021,
Номер
46, С. 102131 - 102131
Опубликована: Сен. 11, 2021
Ferroptosis
plays
a
role
in
several
diseases
such
as
iron
overload-induced
liver
diseases.
Manipulation
of
ferroptosis
has
been
explored
potential
therapeutic
strategy
to
treat
related
Numerous
antioxidants
have
identified
control
but
the
cell-autonomous
mechanisms
responsible
for
regulating
remain
elusive.
In
present
study,
we
found
that
overload
promoted
hepatocytes
by
excessively
inducing
HO-1
expression,
which
contributed
progression
injury
and
fibrosis,
accompanied
upregulation
FGF21
protein
level
vitro
vivo.
Interestingly,
both
recombinant
Fgf21
overexpression
significantly
protected
against
mitochondria
damage,
fibrosis
inhibiting
ferroptosis.
contrast,
loss
aggravated
Notably,
FGF21-induced
inhibition
(via
promotion
ubiquitination
degradation)
NRF2
activation
provide
mechanistic
explanation
this
phenomenon.
Taken
together,
novel
suppressor.
Thus,
may
an
effective
treatment
ferroptosis-related
diseases,
hereditary
haemochromatosis
(HH).
Redox Biology,
Год журнала:
2019,
Номер
23, С. 101107 - 101107
Опубликована: Янв. 12, 2019
The
transcription
factor
nuclear
erythroid
2-related
2
(NRF2)
is
a
key
regulator
of
the
cellular
antioxidant
response,
controlling
expression
genes
that
counteract
oxidative
and
electrophilic
stresses.
Many
pathological
conditions
are
linked
to
imbalances
in
redox
homeostasis,
illustrating
important
role
defense
systems
preventing
pathogenic
effects
associated
with
accumulation
reactive
species.
In
particular,
it
becoming
increasingly
apparent
lipid
peroxides
has
an
driving
pathogenesis
multiple
disease
states.
A
example
this
recent
discovery
novel
form
cell
death
termed
ferroptosis.
Ferroptosis
iron-dependent,
peroxidation-driven
cascade
become
target
development
anti-cancer
therapies,
as
well
prevention
neurodegenerative
cardiovascular
diseases.
review,
we
will
provide
brief
overview
peroxidation,
components
involved
ferroptotic
cascade.
We
also
highlight
NRF2
signaling
pathway
mediating
peroxidation
ferroptosis,
focusing
on
established
mitigate
these
pathways,
relevance
NRF2-lipid
peroxidation-ferroptosis
axis
disease.
International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(13), С. 4777 - 4777
Опубликована: Июль 6, 2020
Nuclear
factor
erythroid
2-related
2
(NRF2)
is
a
transcription
that
regulates
the
cellular
defense
against
toxic
and
oxidative
insults
through
expression
of
genes
involved
in
stress
response
drug
detoxification.
NRF2
activation
renders
cells
resistant
to
chemical
carcinogens
inflammatory
challenges.
In
addition
antioxidant
responses,
many
other
processes,
including
metabolism
inflammation,
its
functions
are
beyond
originally
envisioned.
activity
tightly
regulated
complex
transcriptional
post-translational
network
enables
it
orchestrate
cell’s
adaptation
various
pathological
stressors
for
homeostasis
maintenance.
Elevated
or
decreased
by
pharmacological
genetic
manipulations
associated
with
metabolism-
inflammation-related
diseases.
Emerging
evidence
shows
lies
at
center
regulatory
establishes
as
truly
pleiotropic
factor.
Here
we
summarize
roles
metabolic
reprogramming,
unfolded
protein
response,
proteostasis,
autophagy,
mitochondrial
biogenesis,
immunity.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Фев. 3, 2021
Abstract
Ferroptosis
is
an
iron-dependent
cell
death,
which
different
from
apoptosis,
necrosis,
autophagy,
and
other
forms
of
death.
The
process
ferroptotic
death
defined
by
the
accumulation
lethal
lipid
species
derived
peroxidation
lipids,
can
be
prevented
iron
chelators
(e.g.,
deferiprone,
deferoxamine)
small
lipophilic
antioxidants
ferrostatin,
liproxstatin).
This
review
summarizes
current
knowledge
about
regulatory
mechanism
ferroptosis
its
association
with
several
pathways,
including
iron,
lipid,
cysteine
metabolism.
We
have
further
discussed
contribution
to
pathogenesis
diseases
such
as
cancer,
ischemia/reperfusion,
various
neurodegenerative
Alzheimer’s
disease
Parkinson’s
disease),
evaluated
therapeutic
applications
inhibitors
in
clinics.
Molecules,
Год журнала:
2020,
Номер
25(22), С. 5474 - 5474
Опубликована: Ноя. 23, 2020
Inflammation
is
a
key
driver
in
many
pathological
conditions
such
as
allergy,
cancer,
Alzheimer’s
disease,
and
others,
the
current
state
of
available
drugs
prompted
researchers
to
explore
new
therapeutic
targets.
In
this
context,
accumulating
evidence
indicates
that
transcription
factor
Nrf2
plays
pivotal
role
controlling
expression
antioxidant
genes
ultimately
exert
anti-inflammatory
functions.
its
principal
negative
regulator,
E3
ligase
adaptor
Kelch-like
ECH-
associated
protein
1
(Keap1),
play
central
maintenance
intracellular
redox
homeostasis
regulation
inflammation.
Interestingly,
proved
contribute
heme
oxygenase-1
(HO-1)
axis,
which
potent
target.
Recent
studies
showed
connection
between
Nrf2/antioxidant
response
element
(ARE)
system
inflammatory
mediators,
NF-κB
pathway
macrophage
metabolism.
This
suggests
strategy
for
designing
chemical
agents
modulators
dependent
pathways
target
immune
response.
Therefore,
present
review
will
examine
relationship
signaling
inflammation
well
possible
approaches
modulation
pathway.
Annual Review of Cancer Biology,
Год журнала:
2018,
Номер
3(1), С. 35 - 54
Опубликована: Окт. 25, 2018
Ferroptosis
is
a
nonapoptotic,
iron-dependent
form
of
cell
death
that
can
be
activated
in
cancer
cells
by
natural
stimuli
and
synthetic
agents.
Three
essential
hallmarks
define
ferroptosis,
namely:
the
loss
lipid
peroxide
repair
capacity
phospholipid
hydroperoxidase
GPX4,
availability
redox-active
iron,
oxidation
polyunsaturated
fatty
acid
(PUFA)-containing
phospholipids.
Several
processes
including
RAS/MAPK
signaling,
amino
iron
metabolism,
ferritinophagy,
epithelial-to-mesenchymal
transition,
adhesion,
mevalonate
biosynthesis
modulate
susceptibility
to
ferroptosis.
sensitivity
also
governed
p53
KEAP1/NRF2
activity,
linking
ferroptosis
function
key
tumor
suppressor
pathways.
Together
these
findings
highlight
role
as
an
emerging
concept
biology
attractive
target
for
precision
medicine
discovery.
Frontiers in Neuroscience,
Год журнала:
2020,
Номер
14
Опубликована: Апрель 21, 2020
Ferroptosis
is
a
kind
of
regulated
cell
death
(RCD)
caused
by
the
redox
state
disorder
intracellular
microenvironment
controlled
glutathione
peroxidase
4
(GPX4),
which
inhibited
iron
chelators
and
lipophilic
antioxidants.
In
addition
to
classical
regulatory
mechanisms,
new
factors
for
ferroptosis
have
been
discovered
in
recent
years,
such
as
P53
pathway,
ATF3/4
Beclin
1
(BECN1)
some
non-coding
RNA.
closely
related
cancer
treatment,
neurodegenerative
diseases,
ischemia-reperfusion
organ,
neurotoxicity,
other
particular,
field
diseases
treatment
has
aroused
people's
interest.
The
nuclear
factor
E2
2
(Nrf2/NFE2L2)
proved
play
key
role
neurodegeneration
disease
regulation.
promotes
progression
while
expression
Nrf2
its
target
genes
(Ho-1,
Nqo-1,
Trx)
declined
with
aging,
therefore,
there
still
insufficient
evidence
networks
diseases.
this
review,
we
will
provide
brief
overview
well
an
emphasis
on
mechanism
regulating
ferroptosis.
We
also
highlight
during
process
investigate
theoretical
basis
further
research
relationship
between
treatment.
Cell Death and Differentiation,
Год журнала:
2022,
Номер
29(3), С. 467 - 480
Опубликована: Янв. 24, 2022
Ferroptosis
is
an
iron-dependent
form
of
non-apoptotic
cell
death
characterized
by
excessive
lipid
peroxidation
and
associated
with
a
plethora
pathological
conditions
in
the
liver.
Emerging
evidence
supports
notion
that
dysregulated
metabolic
pathways
impaired
iron
homeostasis
play
role
progression
liver
disease
via
ferroptosis.
Although
molecular
mechanisms
which
ferroptosis
causes
are
poorly
understood,
several
ferroptosis-associated
genes
have
been
implicated
disease.
Here,
we
review
physiological
processing
nutrients,
our
current
understanding
metabolism,
characteristics
ferroptosis,
regulate
In
addition,
summarize
pathogenesis
disease,
including
injury,
non-alcoholic
steatohepatitis,
fibrosis,
cirrhosis,
hepatocellular
carcinoma.
Finally,
discuss
therapeutic
potential
targeting
for
managing
