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:
2020,
Номер
21(8), С. 2951 - 2951
Опубликована: Апрель 22, 2020
Over
10%
of
the
global
population
suffers
from
kidney
disease.
However,
only
replacement
therapies,
which
burden
medical
expenses,
are
currently
effective
in
treating
Therefore,
elucidating
complicated
molecular
pathology
disease
is
an
urgent
priority
for
developing
innovative
therapeutics
Recent
studies
demonstrated
that
intertwined
renal
vasculature
often
causes
ischemia-reperfusion
injury
(IRI),
generates
oxidative
stress,
and
accumulation
stress
a
common
pathway
underlying
various
types
We
reported
activating
antioxidative
transcription
factor
Nrf2
tubules
mice
with
IRI
effectively
mitigates
tubular
damage
interstitial
fibrosis
by
inducing
expression
genes
related
to
cytoprotection
against
stress.
Additionally,
since
performs
multiple
functions
beyond
blood
purification,
renoprotection
activation
anticipated
lead
benefits.
Indeed,
our
experiments
indicated
possibility
anemia,
caused
impaired
production
erythroid
growth
erythropoietin
injured
kidneys,
moderates
organ
worsened
anemic
hypoxia.
Clinical
trials
investigating
Nrf2-activating
compounds
patients
ongoing,
beneficial
effects
being
obtained.
Thus,
activators
expected
emerge
as
first-in-class
medicine
treatment.
Neurobiology of Disease,
Год журнала:
2020,
Номер
145, С. 105061 - 105061
Опубликована: Авг. 28, 2020
Glycerol-based
ether
lipids
including
phospholipids
form
a
specialized
branch
of
that
in
mammals
require
peroxisomes
for
their
biosynthesis.
They
are
major
components
biological
membranes
and
one
particular
subgroup,
the
plasmalogens,
is
widely
regarded
as
cellular
antioxidant.
Their
vast
potential
to
influence
signal
transduction
pathways
less
well
known.
Here,
we
summarize
literature
showing
associations
with
essential
signaling
cascades
wide
variety
lipids,
platelet-activating
factor,
alkylglycerols,
ether-linked
lysophosphatidic
acid
plasmalogen-derived
polyunsaturated
fatty
acids.
The
available
experimental
evidence
demonstrates
links
several
common
players
like
protein
kinase
C,
peroxisome
proliferator-activated
receptors
or
mitogen-activated
kinases.
Furthermore,
lipid
levels
have
repeatedly
been
connected
some
most
abundant
neurological
diseases,
particularly
Alzheimer's
disease
more
recently
also
neurodevelopmental
disorders
autism.
Thus,
critically
discuss
role
these
compounds
etiology
pathophysiology
diseases
an
emphasis
on
processes.
Finally,
review
emerging
interest
plasmalogens
treatment
target
assessing
data
highlighting
future
perspectives.
Although
many
aspects
involvement
identified
vitro
still
be
confirmed
vivo,
compiled
show
intriguing
properties
contributions
health
will
trigger
further
research.
Biomedicine & Pharmacotherapy,
Год журнала:
2020,
Номер
129, С. 110373 - 110373
Опубликована: Июнь 27, 2020
A
salient
pathological
features
in
Alzheimer's
disease
includes
redox
impairment
and
neuroinflammation.
Nuclear
factor
erythroid
2-related
2
(Nrf2)
kappa
B
(NF-ҡB)
are
the
two
key
transcription
factors
that
regulate
cellular
responses
to
neuroinflammation
respectively.
An
effective
way
confer
neuroprotection
central
nervous
system
(CNS)
is
activation
of
a
i.e
(Nrf2).
enhancer
element
known
as
Antioxidant
Response
Element
(ARE)
mediates
expression
phase
II
detoxification
enzymes.
Nrf2
nuclear
binds
ARE
thereby
transcribing
several
antioxidant
genes.
Kelch
ECH
associating
protein-1
(Keap1),
culin
3-based
E3
ligase,
polyubiquitinates
targets
it
for
its
degradation.
Disruption
interaction
between
Keap1/Nrf2
can
increase
brain's
endogenous
capacity
responsible
cell
defence
against
oxidative
stress
(AD).
The
current
review
discusses
about
Keap1-Nrf2-ARE
structure
function
with
special
emphasis
on
various
pathways
involved
positive
negative
modulation
Nrf2,
namely
Phosphoinositide
3-
kinase
(PI3K),
Glycogen
synthase
kinase-3β
(GSK-3β),
kappa-b
(NF-ҡb),
Janus
kinase/signal
transducer
activator
(JAK-STAT),Tumour
Necrosis
Factor-
α
(TNF-α),
p38Mitogen-activated
protein
kinases
(p38MAPK),
Cyclic
AMP
response
binding
(CREB)
intrinsic
&
extrinsic
apoptotic
pathway.
Furthermore,
this
highlights
miscellaneous
activators
promising
therapeutic
agents
slowingdown
progression
AD.
Antioxidants,
Год журнала:
2021,
Номер
10(3), С. 349 - 349
Опубликована: Фев. 26, 2021
Doxorubicin
(DOX)
is
extensively
applied
in
cancer
therapy
due
to
its
efficacy
suppressing
progression
and
inducing
apoptosis.
After
discovery,
this
chemotherapeutic
agent
has
been
frequently
used
for
therapy,
leading
chemoresistance.
Due
dose-dependent
toxicity,
high
concentrations
of
DOX
cannot
be
administered
patients.
Therefore,
experiments
have
directed
towards
revealing
underlying
mechanisms
responsible
resistance
ameliorating
adverse
effects.
Nuclear
factor
erythroid
2-related
2
(Nrf2)
signaling
activated
increase
levels
reactive
oxygen
species
(ROS)
cells
protect
them
against
oxidative
stress.
It
reported
that
Nrf2
activation
associated
with
drug
resistance.
In
exposed
DOX,
stimulation
protects
cell
death.
Various
upstream
mediators
regulate
Strategies,
both
pharmacological
genetic
interventions,
reversing
However,
induction
importance
alleviating
side
effects
DOX.
Pharmacological
agents
naturally
occurring
compounds
as
the
most
common
amelioration.
Furthermore,
networks
which
a
key
player
protection
revealed
are
discussed
current
review.
Antioxidants,
Год журнала:
2021,
Номер
10(12), С. 1929 - 1929
Опубликована: Ноя. 30, 2021
Aging
is
inevitable,
but
the
inherently
and
genetically
programmed
aging
process
markedly
influenced
by
environmental
factors.
All
organisms
are
constantly
exposed
to
various
stresses,
either
exogenous
or
endogenous,
throughout
their
lives,
quality
quantity
of
stresses
generate
diverse
impacts
on
organismal
process.
In
current
oxygenic
atmosphere
earth,
oxidative
stress
caused
reactive
oxygen
species
one
most
common
critical
factors
for
life.
The
Kelch-like
ECH-associated
protein
1-NFE2-related
factor
2
(KEAP1-NRF2)
system
a
defense
mechanism
cells
in
response
redox
perturbations.
presence
electrophilic
insults,
thiol
moieties
cysteine
KEAP1
modified,
consequently
NRF2
activates
its
target
genes
detoxification
cytoprotection.
A
number
studies
have
clarified
contributions
KEAP1-NRF2
prevention
attenuation
physiological
aging-related
diseases.
Accumulating
knowledge
control
stress-induced
damage
may
provide
clue
extending
healthspan
treating
this
review,
we
focus
relationships
between
alterations
sensory,
glandular,
muscular,
central
nervous
systems
roles
processes.
The Annual Review of Pharmacology and Toxicology,
Год журнала:
2021,
Номер
62(1), С. 255 - 277
Опубликована: Окт. 12, 2021
Neurodegenerative
diseases
are
characterized
by
the
loss
of
homeostatic
functions
that
control
redox
and
energy
metabolism,
neuroinflammation,
proteostasis.
The
transcription
factor
nuclear
erythroid
2–related
2
(NRF2)
is
a
master
controller
these
functions,
its
overall
activity
compromised
during
aging
in
diseases.
However,
NRF2
can
be
activated
pharmacologically
now
being
considered
common
therapeutic
target.
Many
gaps
still
exist
our
knowledge
specific
role
plays
specialized
brain
cell
or
how
cells
respond
to
hallmarks
This
review
discusses
relevance
several
hallmark
features
neurodegenerative
current
status
pharmacological
activators
might
pass
through
blood-brain
barrier
provide
disease-modifying
effect.
Redox Biology,
Год журнала:
2022,
Номер
58, С. 102525 - 102525
Опубликована: Окт. 28, 2022
Oxidative
stress
is
an
essential
component
in
the
progression
of
diabetic
kidney
disease
(DKD),
and
transcription
factor
NF-E2-related
factor-2
(Nrf2)
plays
critical
roles
protecting
body
against
oxidative
stress.
To
clarify
Nrf2
DKD,
this
study
we
prepared
compound
mutant
mice
with
diabetes
loss
antioxidative
defense.
Specifically,
Ins2Akita/+
(Akita)
knockout
(Akita::Nrf2−/−)
or
Akita
induction
(Akita::Keap1FA/FA)
mice.
Eighteen-week-old
Akita::Nrf2−/−
showed
more
severe
symptoms
than
In
mouse
kidneys,
glomeruli
distended
capillary
loops,
suggesting
enhanced
mesangiolysis.
Distal
tubules
dilation
increase
8-hydroxydeoxyguanosine-positive
staining.
expression
glutathione
(GSH)
synthesis-related
genes
was
decreased,
actual
GSH
level
decreased
matrix-assisted
laser
desorption/ionization
mass
spectrometry
imaging
analysis.
exhibited
inflammation
enhancement
infiltrated
macrophages
kidney.
further
examine
compared
forty-week-old
compounds
Nrf2-knockout
mildly
induced
displayed
medullary
cast
formation,
but
formation
ameliorated
Akita::Keap1FA/FA
Moreover,
mice,
tubule
injury
inflammation-related
gene
were
significantly
suppressed,
which
evident
kidneys.
These
results
demonstrate
that
contributes
to
protection
kidneys
DKD
by
suppressing
inflammation.
Biomedicine & Pharmacotherapy,
Год журнала:
2022,
Номер
152, С. 113248 - 113248
Опубликована: Июнь 10, 2022
Alzheimer's
disease
(AD)
is
a
neurodegenerative
with
amyloid
beta
(Aβ)
deposition
and
intracellular
neurofibrillary
tangles
(NFTs)
as
its
characteristic
pathological
changes.
Ameliorating
oxidative
stress
inflammation
has
become
new
trend
in
the
prevention
treatment
of
AD.
Dioscin,
natural
steroidal
saponin
which
exists
Dioscoreae
nipponicae
rhizomes,
displays
various
pharmacological
activities,
but
role
still
unknown.
In
present
work,
effect
dioscin
on
AD
was
evaluated
injured
SH-SY5Y
cells
induced
by
H2O2
C57BL/6
mice
challenged
AlCl₃
combined
D-galactose.
Results
showed
that
obviously
increased
cell
viability
decreased
reactive
oxygen
species
(ROS)
level
cells.
vivo,
improved
spatial
learning
memory
abilities
well
gait
interlimb
coordination
disorders
Moreover,
distinctly
restored
levels
malondialdehyde
(MDA),
superoxide
dismutase
(SOD),
42
(Aβ42),
acetylcholine
(ACh)
acetylcholinesterase
(AChE)
mice,
reversed
histopathological
changes
brain
tissue.
Mechanism
studies
revealed
markedly
down-regulated
expression
RAGE
NOX4.
Subsequently,
up-regulated
Nrf2
HO-1
related
to
stress,
p-NF-κB(p-p65)/NF-κB(p65),
AP-1
inflammatory
factors
involved
pathway.
siRNAs
transfection
further
clarified
activity
achieved
regulating
RAGE/NOX4
conclusion,
excellent
anti-AD
adjusting
RAGE/NOX4-mediated
inflammation,
provided
basis
for
research
development
against
Frontiers in Aging Neuroscience,
Год журнала:
2022,
Номер
14
Опубликована: Сен. 7, 2022
Alzheimer's
disease
(AD)
is
a
multifaceted
neurodegenerative
disorder
with
many
complex
pathways
feeding
into
its
pathogenesis
and
progression.
Vitamin
C,
an
essential
dietary
antioxidant,
vital
for
proper
neurological
development
maintenance.
This
meta-analysis
systematic
review
attempted
to
define
the
relationship
between
vitamin
C
plasma
levels
AD
while
highlighting
importance
involvement
of
in
AD.PRISMA
guidelines
were
used
obtain
studies
quantifying
control
subjects.
The
literature
was
searched
online
databases
PubMed,
Google
Scholar,
Web
Science.
A
total
12
included
(n
=
1,100)
analyzed
using
Comprehensive
Meta-Analysis
3.0.The
results
show
that
there
significant
decrease
patients
as
compared
healthy
controls
(pooled
SMD
random-effect
model:
-1.164,
95%CI:
-1.720
-0.608,
Z
-4.102,
p
0.00)
heterogeneity
(I2
93.218).
sensitivity
analysis
showed
directionally
similar
results.
Egger's
regression
test
(p
0.11)
visual
inspection
funnel
plot
no
publication
bias.Based
on
these
studies,
it
can
be
deduced
deficiency
involved
progression
supplementation
plausible
preventive
treatment
strategy.
However,
clinical
are
warranted
elucidate
exact
mechanistic
role
pathophysiology
prevention.
