Biomolecules,
Год журнала:
2023,
Номер
13(3), С. 549 - 549
Опубликована: Март 17, 2023
Alzheimer’s
disease
(AD)
is
a
common
neurodegenerative
disorder
that
affects
the
elderly.
One
of
key
features
AD
accumulation
reactive
oxygen
species
(ROS),
which
leads
to
an
overall
increase
in
oxidative
damage.
The
nuclear
factor
(erythroid-derived
2)-like
2
(Nrf2)
master
regulator
antioxidant
response
cells.
Under
low
ROS
levels,
Nrf2
kept
cytoplasm.
However,
production
translocation
into
nucleus,
where
it
activates
transcription
several
genes
involved
cells’
response.
Additionally,
activation
increases
autophagy
function.
AD,
Aβ
and
tau
reduces
decreasing
reduced
levels
contribute
further
by
impairing
their
autophagy-mediated
turnover.
In
this
review,
we
discuss
overwhelming
evidence
indicating
genetic
or
pharmacological
as
potential
approach
mitigate
pathology.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(13), С. 7273 - 7273
Опубликована: Июнь 30, 2022
Ageing
and
chronic
degenerative
pathologies
demonstrate
the
shared
characteristics
of
high
bioavailability
reactive
oxygen
species
(ROS)
oxidative
stress,
chronic/persistent
inflammation,
glycation,
mitochondrial
abnormalities.
Excessive
ROS
production
results
in
nucleic
acid
protein
destruction,
thereby
altering
cellular
structure
functional
outcome.
To
stabilise
increased
modulate
human
body
produces
antioxidants,
“free
radical
scavengers”,
that
inhibit
or
delay
cell
damage.
Reinforcing
antioxidant
defence
system
and/or
counteracting
deleterious
repercussions
immoderate
nitrogen
(RONS)
is
critical
may
curb
progression
ageing
syndromes.
Various
therapeutic
methods
for
stress
reduction
have
been
developed.
However,
scientific
investigations
are
required
to
assess
their
efficacy.
In
this
review,
we
summarise
interconnected
mechanism
inflammation
contributes
pathologies,
including
neurodegenerative
diseases,
such
as
Alzheimer’s
disease
(AD)
Parkinson’s
(PD),
cardiovascular
diseases
CVD,
diabetes
mellitus
(DM),
kidney
(CKD).
We
also
highlight
potential
counteractive
measures
combat
diseases.
Essays in Biochemistry,
Год журнала:
2021,
Номер
65(7), С. 925 - 940
Опубликована: Окт. 10, 2021
Ferroptosis
is
an
iron-
and
lipid
peroxidation-dependent
cell
death
modality
emerging
evidence
indicates
that
ferroptosis
has
great
explanatory
potential
for
neuronal
loss
associated
CNS
dysfunction
in
a
range
of
neurodegenerative
diseases
(e.g.,
Alzheimer's,
Parkinson's
Huntington's
diseases,
Motor
neuron
disease,
Friedreich
ataxia
(FRDA)).
Ferroptotic
results
from
lethal
levels
phospholipid
hydroperoxides
are
generated
by
iron-dependent
peroxidation
polyunsaturated
fatty
acids
(PUFAs),
such
as
arachidonic
adrenic
acids,
which
conjugated
to
specific
phospholipids
phosphatidylethanolamines
(PEs)).
The
major
cellular
protector
against
glutathione
peroxidase
4
(GPX4),
membrane-associated
selenoenzyme
reduces
deleterious
their
corresponding
benign
alcohols
glutathione-dependent
manner.
Other
complementary
protective
systems
have
also
been
identified
act
bolster
defences
ferroptosis.
Many
pharmacological
modulators
the
pathway
identified,
targeting
proteins
involved
iron
homoeostasis
autophagy;
production
detoxification
peroxides,
cyst(e)ine/glutathione
metabolism.
While
growing
number
signalling
pathways
converge
regulate
cascade,
understanding
regulation
suggests
ferroptotic
'tone'
cells
can
be
set
transcription
factor,
nuclear
factor
erythroid
2-related
2
(NRF2),
transcriptionally
controls
many
key
components
pathway.
In
this
review,
we
provide
critical
overview
relationship
between
NRF2
signalling.
With
focus
on
role
Alzheimer's
disease
(AD),
discuss
how
therapeutic
modulation
viable
strategy
explore
treatment
ferroptosis-driven
neurodegeneration.
Frontiers in Neuroscience,
Год журнала:
2022,
Номер
16
Опубликована: Март 31, 2022
Since
1995,
more
than
100
transgenic
(Tg)
mouse
models
of
Alzheimer's
disease
(AD)
have
been
generated
in
which
mutant
amyloid
precursor
protein
(APP)
or
APP/presenilin
1
(PS1)
cDNA
is
overexpressed
(
Cardiovascular Therapeutics,
Год журнала:
2022,
Номер
2022, С. 1 - 11
Опубликована: Июль 15, 2022
Diabetes
causes
lipid
peroxide
to
accumulate
within
cardiomyocytes.
Furthermore,
buildup
is
a
risk
factor
for
ferroptosis.
This
study
aimed
at
examining
whether
curcumin
can
ameliorate
ferroptosis
in
the
treatment
of
diabetic
cardiomyopathy.
Hematoxylin
and
eosin
Masson
sections
were
used
examine
morphology,
arrangement,
degree
fibrosis
myocardium
rabbit
models.
The
expression
levels
nuclear
Nrf2,
Gpx4,
Cox1,
Acsl4
animal
cell
models
quantitatively
analyzed
using
immunofluorescence
western
blotting.
Nrf2-overexpression
lentivirus
vectors
transfected
into
cardiomyocytes,
protective
effects
Nrf2
on
cardiomyocytes
under
high
glucose
stimulation
assessed
terminal
deoxynucleotidyl
transferase
dUTP
nick-end
labelling
reactive
oxygen
species
probes.
was
found
disorder
myocardial
arrangement
significantly
increase
collagen
cells.
Curcumin
transfer
Gpx4
HO-1,
reduce
induced
damage,
reverse
damage
caused
by
inducer
erastin.
confirmed
that
promote
translocation
oxidative
scavenging
factors,
such
as
excessive
loss,
inhibit
glucose-induced
highlights
potentially
new
therapeutic
route
investigation
Physiological Reviews,
Год журнала:
2023,
Номер
104(1), С. 103 - 197
Опубликована: Окт. 16, 2023
Alzheimer
disease
(AD)
is
associated
with
multiple
etiologies
and
pathological
mechanisms,
among
which
oxidative
stress
(OS)
appears
as
a
major
determinant.
Intriguingly,
OS
arises
in
various
pathways
regulating
brain
functions,
it
seems
to
link
different
hypotheses
mechanisms
of
AD
neuropathology
high
fidelity.
The
particularly
vulnerable
damage,
mainly
because
its
unique
lipid
composition,
resulting
an
amplified
cascade
redox
reactions
that
target
several
cellular
components/functions
ultimately
leading
neurodegeneration.
present
review
highlights
the
“OS
hypothesis
AD,”
including
amyloid
beta-peptide-associated
role
protein
oxidation
unraveled
by
proteomics,
antioxidant
strategies
have
been
investigated
modulate
progression
AD.
Collected
studies
from
our
groups
others
contributed
unraveling
close
relationships
between
perturbation
homeostasis
elucidating
redox-regulated
events
potentially
involved
both
pathogenesis
However,
complexity
requires
in-depth
understanding
intracellular
affecting
relevant
for
functions.
This
crucial
developing
pharmacological
targeting
OS-mediated
toxicity
may
contribute
slow
well
improve
quality
life
persons
this
severe
dementing
disorder.
Antioxidants and Redox Signaling,
Год журнала:
2023,
Номер
38(13-15), С. 974 - 988
Опубликована: Март 17, 2023
Significance:
Central
nervous
system
(CNS)
diseases
are
disorders
of
the
brain
and/or
spinal
cord
and
include
neurodegenerative
such
as
Alzheimer's
disease,
Parkinson's
multiple
sclerosis.
Nuclear
factor
erythroid
2-related
2
(NRF2)
is
a
transcription
belonging
to
cap-n-collar
family
that
harbors
unique
basic
leucine
zipper
motif
plays
master
regulator
homeostatic
responses.
Recent
Advances:
Kelch-like
ECH-associated
protein
1
(KEAP1)
an
adaptor
Cullin3
(CUL3)-based
ubiquitin
E3
ligase
enhances
ubiquitylation
NRF2,
which
promotes
degradation
NRF2
suppress
its
transcriptional
activity
in
absence
stress.
Cysteine
residues
KEAP1
modified
under
stress
conditions,
attenuated,
allowing
it
accumulate
induce
expression
target
genes.
This
regulatory
referred
KEAP1-NRF2
central
role
protecting
cells
against
various
stresses.
also
negatively
regulates
inflammatory
cytokine
chemokine
genes
suppresses
pathological
inflammation.
As
oxidative
stress,
inflammation,
proteostasis
known
contribute
diseases,
attractive
for
treatment
these
diseases.
Critical
Issues:
In
mouse
models
Nrf2
depletion
exacerbates
symptoms
damage
inflammation
CNS.
contrast,
chemical
or
genetic
activation
improves
symptoms.
Indeed,
NRF2-activating
dimethyl
fumarate
now
widely
used
clinical
MS.
Future
Directions:
The
promising
therapeutic
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(33)
Опубликована: Авг. 7, 2023
Neuroinflammation
is
a
common
feature
of
neurodegenerative
disorders
such
as
Alzheimer's
disease
(AD).
induced
by
dysregulated
glial
activation,
and
astrocytes,
the
most
abundant
cells,
become
reactive
upon
neuroinflammatory
cytokines
released
from
microglia
actively
contribute
to
neuronal
loss.
Therefore,
blocking
astrocyte
functions
viable
strategy
manage
disorders.
However,
factors
or
therapeutics
directly
regulating
subtypes
remain
unexplored.
Here,
we
identified
transcription
factor
NF-E2-related
2
(Nrf2)
therapeutic
target
in
neurotoxic
astrocytes
neuroinflammation.
We
found
that
absence
Nrf2
promoted
activation
brain
tissue
samples
obtained
AD
model
5xFAD
mice,
whereas
enhanced
expression
blocked
induction
gene
counteracting
NF-κB
subunit
p65
recruitment.
Neuroinflammatory
robustly
up-regulated
genes
associated
with
type
I
interferon
antigen-presenting
pathway,
which
were
suppressed
pathway
activation.
Moreover,
impaired
cognitive
behaviors
observed
mice
rescued
ALGERNON2
treatment,
potentiated
reduced
astrocytes.
Thus,
highlight
potential
astrocyte-targeting
therapy
promoting
signaling
for
neuroinflammation-triggered
neurodegeneration.
