Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment
Ageing Research Reviews,
Год журнала:
2024,
Номер
101, С. 102480 - 102480
Опубликована: Сен. 3, 2024
Mitochondria
functionally
degrade
as
neurons
age.
Degenerative
changes
cause
inefficient
oxidative
phosphorylation
(OXPHOS)
and
elevated
electron
leakage
from
the
transport
chain
(ETC)
promoting
increased
intramitochondrial
generation
of
damaging
reactive
oxygen
nitrogen
species
(ROS
RNS).
The
associated
progressive
accumulation
molecular
damage
causes
an
increasingly
rapid
decline
in
mitochondrial
physiology
contributing
to
aging.
Melatonin,
a
multifunctional
free
radical
scavenger
indirect
antioxidant,
is
synthesized
matrix
neurons.
Melatonin
reduces
ETC
elevates
ATP
production;
it
also
detoxifies
ROS/RNS
via
SIRT3/FOXO
pathway
upregulates
activities
superoxide
dismutase
2
glutathione
peroxidase.
influences
glucose
processing
by
In
neurogenerative
diseases,
often
adopt
Warburg-type
metabolism
which
excludes
pyruvate
mitochondria
causing
reduced
acetyl
coenzyme
A
production.
Acetyl
supports
citric
acid
cycle
OXPHOS.
Additionally,
required
co-substrate
for
arylalkylamine-N-acetyl
transferase,
rate
limits
melatonin
synthesis;
therefore,
production
diminished
cells
that
experience
making
more
vulnerable
stress.
Moreover,
endogenously
produced
diminishes
during
aging,
further
increasing
components.
More
normal
preserved
aging
with
supplementation.
Язык: Английский
Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders
Antioxidants,
Год журнала:
2024,
Номер
13(4), С. 449 - 449
Опубликована: Апрель 10, 2024
Peroxiredoxin
6
(Prdx6),
a
unique
1-Cys
member
of
the
peroxiredoxin
family,
exhibits
peroxidase
activity,
phospholipase
and
lysophosphatidylcholine
acyltransferase
(LPCAT)
activity.
Prdx6
has
been
known
to
be
an
important
enzyme
for
maintenance
lipid
peroxidation
repair,
cellular
metabolism,
inflammatory
signaling,
antioxidant
damage.
Growing
research
demonstrated
that
altered
activity
this
is
linked
with
various
pathological
processes
including
central
nervous
system
(CNS)
disorders.
This
review
discusses
distinctive
structure,
function
in
different
CNS
disorders,
as
well
emphasizing
significance
neurological
Язык: Английский
Melatonin Mitigates Acidosis-Induced Neuronal Damage by Up-Regulating Autophagy via the Transcription Factor EB
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1170 - 1170
Опубликована: Янв. 29, 2025
Acidosis,
a
common
feature
of
cerebral
ischemia
and
hypoxia,
results
in
neuronal
damage
death.
This
study
aimed
to
investigate
the
protective
effects
mechanisms
action
melatonin
against
acidosis-induced
damage.
SH-SY5Y
cells
were
exposed
an
acidic
environment
simulate
acidosis,
photothrombotic
(PT)
infarction
model
was
used
establish
animal
male
C57/BL6J
mice.
Both
vivo
vitro
studies
demonstrated
that
acidosis
increased
cytoplasmic
transcription
factor
EB
(TFEB)
levels,
reduced
nuclear
TFEB
suppressed
autophagy,
as
evidenced
by
elevated
p62
higher
LC3-II/LC3-I
ratio,
decreased
synapse-associated
proteins
(PSD-95
synaptophysin),
apoptosis.
In
contrast,
promoted
translocation
TFEB,
enhanced
reversed
Moreover,
role
melatonin’s
neuroprotective
validated
modulating
translocation.
conclusion,
mitigates
promoting
thereby
enhancing
autophagy.
These
findings
offer
new
insights
into
potential
treatments
for
acidosis.
Язык: Английский
Melatonin ameliorates ischemic brain injury in experimental stroke by regulation of miR-221 and ATG7 Axis
Biochemical and Biophysical Research Communications,
Год журнала:
2025,
Номер
unknown, С. 151706 - 151706
Опубликована: Март 1, 2025
Язык: Английский
A ROS-responsive, aptamer-targeted graphene oxide nanocomposite for site-specific glutathione release in cerebral ischemia-reperfusion injury
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Май 14, 2025
Cerebral
ischemia-reperfusion
(I/R)
injury
is
a
major
contributor
to
mortality
and
long-term
disability
worldwide,
primarily
due
excessive
reactive
oxygen
species
(ROS)
generation
after
blood
flow
restored.
Although
current
treatments
focus
on
reestablishing
perfusion,
they
offer
limited
protection
against
the
secondary
ROS-mediated
injury.
Here,
we
report
multifunctional
nanocomposite-graphene
oxide
loaded
with
glutathione
(GSH)
functionalized
fibrinogen-targeting
aptamer
(GO@GSH-FA)-capable
of
selectively
releasing
antioxidant
cargo
within
ischemic
brain
microenvironment.
Characterization
revealed
drug-loading
capacity
17.59%
±
3.74%
an
entrapment
efficiency
78.78%
4.55%,
highlighting
robust
loading
GSH.
The
ROS-sensitive
borate
ester
linker
ensures
that
GSH
preferentially
liberated
in
oxidative
stress
regions,
while
fibrinogen
actively
targets
fibrin-rich
thrombotic
sites.
In
vitro,
GO@GSH-FA
significantly
restored
viability
oxygen-glucose-deprived
SH-SY5Y
cells
(from
31%
up
near
control
levels),
reduced
inflammatory
cytokines,
lowered
intracellular
ROS.
Endothelin-1
(ET-1)
induced
cortical
ischemia
model,
led
marked
decrease
neurological
deficit
scores
7.20
1.16
4.20
0.98)
enhanced
neuronal
survival
relative
untreated
animals.
Collectively,
these
findings
underscore
promise
as
targeted,
ROS-responsive
platform
for
mitigating
cerebral
I/R
Язык: Английский
Factors Contributing to Resistance to Ischemia-Reperfusion Injury in Olfactory Mitral Cells
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(11), С. 5079 - 5079
Опубликована: Май 25, 2025
Brain
ischemia-reperfusion
(IR)
injury
is
a
critical
pathological
process
that
leads
to
extensive
neuronal
death,
with
hippocampal
pyramidal
cells,
particularly
those
in
the
cornu
Ammonis
1
(CA1)
subfield,
being
highly
vulnerable.
Until
now,
human
olfactory
mitral
cell
resistance
IR
has
not
been
directly
studied,
but
dysfunction
humans
frequently
reported
systemic
vascular
conditions
such
as
ischemic
heart
failure
and
may
serve
an
early
clinical
marker
of
neurological
or
cardiovascular
disease.
Mitral
principal
neurons
bulb
(OB),
exhibit
remarkable
injury,
suggesting
presence
unique
molecular
adaptations
support
their
survival
under
stress.
Several
factors
contribute
resilience
cells.
They
have
lower
susceptibility
excitotoxicity,
mitigating
harmful
effects
excessive
glutamate
signaling.
Additionally,
they
maintain
efficient
calcium
homeostasis,
preventing
overload—a
major
trigger
for
death
vulnerable
neurons.
cells
also
express
high
baseline
levels
antioxidant
enzymes
activities,
counteracting
oxidative
Their
robust
mitochondrial
function
enhances
energy
production
reduces
metabolic
failure.
Furthermore,
neuroprotective
signaling
pathways,
including
phosphatidylinositol-3-kinase
(PI3K)/Akt,
mitogen-activated
protein
kinase/extracellular
signal-regulated
kinase
(MAPK/ERK),
nuclear
factor
erythroid-2-related
2
(Nrf2)-mediated
antioxidative
responses,
further
bolster
resistance.
In
addition
these
intrinsic
mechanisms,
microvascular
architecture
within
provide
extra
layer
protection.
By
comparing
ischemia-sensitive
neurons,
key
vulnerabilities—such
stress,
dysregulation,
dysfunction—can
be
identified
potentially
mitigated
other
brain
regions.
Understanding
determinants
offer
valuable
insights
developing
novel
strategies
combat
areas,
hippocampus
cortex.
Язык: Английский
Skimmianine Showed Neuroprotection against Cerebral Ischemia/Reperfusion Injury
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(7), С. 7373 - 7385
Опубликована: Июль 12, 2024
The
aim
of
this
study
was
to
investigate
the
antioxidant
and
anti-inflammatory
effects
skimmianine
on
cerebral
ischemia–reperfusion
(IR)
injury.
Twenty-four
female
Wistar
albino
rats
were
randomly
divided
into
three
groups:
Sham,
Ischemia–Reperfusion
(IR),
IR
+
Skimmianine
(40
mg/kg
Skimmianine).
Cerebral
ischemia
induced
using
a
monofilament
nylon
suture
occlude
middle
artery
for
60
min.
Following
23
h
reperfusion,
animals
sacrificed
14
days
later.
brain
tissue
post-IR
injury
examined
through
biochemical
immunochemical
analyses.
In
silico
analysis
Enrichr
platform
explored
skimmianine’s
potential
biological
processes
involving
IBA-1,
IL-6,
NF-κB
proteins.
group,
MDA
levels
increased,
while
SOD
CAT
enzyme
activities
decreased.
treatment
resulted
in
decreased
increased
activities.
Significant
increases
IBA-1
expression
observed
which
significantly
reduced,
modulating
microglial
activation.
High
IL-6
noted
pyramidal
neurons,
vascular
structures,
neuroglial
cells
group;
reduced
expression,
demonstrating
effects.
Increased
neurons
blood
vessels
gray
white
matter
expression.
Gene
Ontology
results
suggest
impacts
immune
inflammatory
responses
via
with
estrogen
mechanisms
mediated
by
NF-κB.
may
be
therapeutic
strategy
due
its
Язык: Английский
Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Май 9, 2024
Background
The
role
of
oxidative
stress
and
inflammation
in
cobalt
(Co)
toxicity
has
been
the
focus
previous
studies.
Cinnamon
its
main
components
have
reported
to
protective
effects
various
tissues
with
antioxidant
anti-inflammatory
effects.
Aims
In
this
study,
effect
cinnamon
extract
(CE)
against
possible
Co-induced
heart,
kidney,
liver
damage
rats
was
investigated
biochemically.
Methods
Eighteen
albino
Wistar
-type
male
were
categorized
into
three
groups
(
n
=
6
per
group):
control
(CG),
CoCL
2
-administered
(CoCL
),
CE
+
(CE
Co)
groups.
group
administered
(100
mg/kg),
CG
distilled
water
orally
by
gavage.
One
hour
after
administration,
Co
(150
mg/kg)
This
procedure
repeated
once
daily
for
7
days.
Then,
biochemical
markers
studied
excised
tissues.
Results
increased
oxidants
proinflammatory
cytokines
decreased
antioxidants
Heart,
tissue
affected
damage.
treatment
suppressed
-induced
increase
decrease
shown
attenuate
cardiac
reducing
serum
troponin
I
(TpI)
creatine
kinase-MB
(CK-MB),
renal
creatinine
blood
urea
nitrogen
(BUN),
alanine
aminotransferase
(ALT)
aspartate
(AST).
Conclusion
induced
production
parameters
depletion
rats.
Our
experimental
results
show
that
protects
inflammatory
changes
CoCLl
.
Язык: Английский
Neuroprotective effects of Hibiscus sabdariffa var. altissima on cerebral ischemia‒Reperfusion injury in rats
Adjia Hamadjida,
Saida Nkuketgnigni Njemguie,
Rigobert Espoir Ayissi Mbomo
и другие.
Pharmacological Research - Modern Chinese Medicine,
Год журнала:
2024,
Номер
12, С. 100485 - 100485
Опубликована: Авг. 2, 2024
Hibiscus
sabdariffa
var.
altissima,
which
is
known
for
its
high-quality
fiber,
commonly
used
in
Traditional
Chinese
Medicine
(TCM)
diuretic,
choleretic,
analgesic,
antitussive,
and
hypotensive
effects.
Furthermore,
the
flowers
have
been
to
treat
diabetes,
hypertension,
atherosclerosis,
obesity.
However,
there
are
no
studies
assessing
neuroprotective
effects
on
cerebral
ischemia,
unlike
variety
Therefore,
this
study
was
aimed
investigate
potential
efficacy
of
altissima
extract
(HAS)
underlying
mechanism
oxidative
stress
neuroinflammation
during
ischemia-reperfusion
(I/R)
injury.
A
model
ischemia
established
male
Wistar
rats
through
middle
artery
occlusion
(MCAO)
reperfusion.
Rats
were
randomly
divided
into
sham,
IR,
IR
+
HSA100,
HSA200,
HSA400
Eda
groups
treated
14
consecutive
days.
The
neurological
deficit
score
cylinder
test
performed
assess
impairment.
Oxidative
determined
by
measuring
levels
malondialdehyde
(MDA)
antioxidant
markers
such
as
reduced
glutathione
(GSH),
superoxide
dismutase
(SOD),
catalase
(CAT)
measured
evaluate
activities.
In
addition,
inflammatory
cytokines,
including
tumor
necrosis
factor-alpha
(TNF-α),
interleukin-1
beta
(IL-1β),
interleukin-6
(IL-6),
also
determined.
Our
results
demonstrated
that
HSA
significantly
ameliorated
impairment
volume
brain
infarct.
decreased
MDA
enhanced
activities
GSH,
SOD
CAT
tissues.
expression
proinflammatory
cytokines
TNF-α,
IL-1β
IL-6
serum.
These
findings
exhibited
a
effect
against
I/R
injury,
possibly
improving
attenuating
responses.
could
be
therapeutic
option
ischemic
injuries.
Язык: Английский