Frontiers in Aging Neuroscience,
Journal Year:
2024,
Volume and Issue:
16
Published: June 11, 2024
Necroptosis
is
implicated
in
the
pathogenesis
of
ischemic
stroke.
However,
mechanism
underlying
sequential
recruitment
receptor-interacting
protein
kinase
1
(RIPK1)
and
N-ethylmaleimide-sensitive
fusion
ATPase
(NSF)
initiating
necroptosis
remains
poorly
understood,
role
NSF
stroke
a
subject
controversy.
Here,
we
utilized
recently
emerging
RNA-targeting
CRISPR
system
known
as
CasRx,
delivered
by
AAVs,
to
knockdown
Neurobiology of Disease,
Journal Year:
2023,
Volume and Issue:
187, P. 106314 - 106314
Published: Oct. 1, 2023
Poly
(ADP-ribose)
polymerase-1
(PARP-1)
is
the
most
extensively
studied
member
of
PARP
superfamily,
with
its
primary
function
being
facilitation
DNA
damage
repair
processes.
Parthanatos
a
type
regulated
cell
death
cascade
initiated
by
PARP-1
hyperactivation,
which
involves
multiple
subroutines,
including
accumulation
ADP-ribose
polymers
(PAR),
binding
PAR
and
apoptosis-inducing
factor
(AIF),
release
AIF
from
mitochondria,
translocation
AIF/macrophage
migration
inhibitory
(MIF)
complex,
massive
MIF-mediated
fragmentation.
Over
past
few
decades,
role
in
central
nervous
system
health
disease
has
received
increasing
attention.
In
this
review,
we
discuss
biological
functions
neural
proliferation
differentiation,
memory
formation,
brain
ageing,
epigenetic
regulation.
We
then
elaborate
on
involvement
PARP-1-dependant
parthanatos
various
neuropathological
processes,
such
as
oxidative
stress,
neuroinflammation,
mitochondrial
dysfunction,
excitotoxicity,
autophagy
damage,
endoplasmic
reticulum
(ER)
stress.
Additional
highlight
contains
PARP-1's
implications
initiation,
progression,
therapeutic
opportunities
for
different
neurological
illnesses,
neurodegenerative
diseases,
stroke,
autism
spectrum
disorder
(ASD),
sclerosis
(MS),
epilepsy,
neuropathic
pain
(NP).
Finally,
emerging
insights
into
repurposing
inhibitors
management
diseases
are
provided.
This
review
aims
to
summarize
exciting
advancements
critical
disorders,
may
open
new
avenues
options
targeting
or
parthanatos.
Acta Neuropathologica,
Journal Year:
2024,
Volume and Issue:
147(1)
Published: Feb. 12, 2024
Abstract
Diseases
of
the
central
nervous
system
(CNS)
are
often
associated
with
vascular
disturbances
or
inflammation
and
frequently
both.
Consequently,
endothelial
cells
macrophages
key
cellular
players
that
mediate
pathology
in
many
CNS
diseases.
Macrophages
brain
consist
CNS-associated
(CAMs)
[also
referred
to
as
border-associated
(BAMs)]
microglia,
both
which
close
neighbours
even
form
direct
contacts
microvessels.
Recent
progress
has
revealed
different
macrophage
populations
a
subset
derived
from
same
erythromyeloid
progenitor
cells.
share
several
common
features
their
life
cycle—from
invasion
into
early
during
embryonic
development
proliferation
CNS,
demise.
In
adults,
microglia
CAMs
have
been
implicated
regulating
patency
diameter
vessels,
blood
flow,
tightness
blood–brain
barrier,
removal
calcification,
life-time
Conversely,
may
affect
polarization
activation
state
myeloid
populations.
The
molecular
mechanisms
governing
pas
de
deux
beginning
be
deciphered
will
reviewed
here.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(4), P. 812 - 812
Published: April 7, 2024
Ischemic
stroke
poses
a
significant
global
health
challenge,
necessitating
ongoing
exploration
of
its
pathophysiology
and
treatment
strategies.
This
comprehensive
review
integrates
various
aspects
ischemic
research,
emphasizing
crucial
mechanisms,
therapeutic
approaches,
the
role
clinical
imaging
in
disease
management.
It
discusses
multifaceted
Netrin-1,
highlighting
potential
promoting
neurovascular
repair
mitigating
post-stroke
neurological
decline.
also
examines
impact
blood–brain
barrier
permeability
on
outcomes
explores
alternative
targets
such
as
statins
sphingosine-1-phosphate
signaling.
Neurocardiology
investigations
underscore
contribution
cardiac
factors
to
mortality,
importance
understanding
brain–heart
axis
for
targeted
interventions.
Additionally,
advocates
early
reperfusion
neuroprotective
agents
counter-time-dependent
excitotoxicity
inflammation,
aiming
preserve
tissue
viability.
Advanced
techniques,
including
DWI,
PI,
MR
angiography,
are
discussed
their
evaluating
penumbra
evolution
guiding
decisions.
By
integrating
molecular
insights
with
modalities,
this
interdisciplinary
approach
enhances
our
offers
promising
avenues
future
research
interventions
improve
patient
outcomes.
Stroke
is
a
global
disease
that
seriously
threatens
human
life.
The
pathological
mechanisms
of
ischemic
stroke
include
neuroinflammation,
oxidative
stress,
and
the
destruction
blood
vessels
at
lesion
site.
Here,
biocompatible
in
situ
hydrogel
platform
was
designed
to
target
multiple
pathogenic
post-stroke,
including
anti-inflammation,
anti-oxidant,
promotion
angiogenesis.
Double-crosslinked
responsive
multifunctional
hydrogels
could
quickly
respond
microenvironment
damage
site
mediate
delivery
nitric
oxide
(NO)
ISO-1
(inhibitor
macrophage
migration
inhibitory
factor,
MIF).
demonstrated
good
biocompatibility
scavenge
reactive
oxygen
species
(ROS)
inflammatory
cytokines,
such
as
interleukin-6
(IL-6),
interleukin-10
(IL-10),
MIF.
In
mouse
model,
hydrogels,
when
situated
within
cerebral
infarction
characterized
by
weak
acidity
elevated
ROS
release,
would
release
anti-inflammatory
nanoparticles
rapidly
exert
an
effect.
Concurrently,
NO
sustained
facilitate
angiogenesis
provide
neuroprotective
effects.
Neurological
function
significantly
improved
treated
mice
assessed
modified
neurological
severity
score,
rotarod
test,
open
field
test.
These
findings
indicate
held
promise
for
alleviate
injury
responding
brain's
microenvironment.
ABSTRACT
Background
Vascular
dementia
(VaD)
includes
a
group
of
brain
disorders
that
are
characterized
by
cerebrovascular
pathology.Neuroinflammation,
disruption
the
blood–brain
barrier
(BBB)
permeability,
white
matter
lesions,
and
neuronal
loss
all
significant
pathological
manifestations
VaD
play
key
role
in
disease
progression.
Necroptosis,
also
known
asprogrammed
necrosis,
is
mode
programmed
cell
death
distinct
from
apoptosis
closely
associated
with
ischemic
injury
neurodegenerative
diseases.
Recent
studies
have
shown
necroptosis
exacerbates
BBB
destruction,
activates
neuroinflammation,
promotes
loss,
severely
affects
prognosis.
Results
Conclusions
In
this
review,
we
outline
roles
its
molecular
mechanisms
process
VaD,
particular
focus
on
modulating
neuroinflammation
exacerbating
permeability
elaborate
regulatory
centrally
involved
cells
mediated
tumor
necrosis
factor‐α
VaD.
We
analyze
possibility
specific
strategy
targeting
would
help
inhibit
destruction
With
necroptosis,
study
delved
into
impact
changes
prognosis
to
provide
new
treatment
ideas.
MedComm,
Journal Year:
2025,
Volume and Issue:
6(3)
Published: Feb. 18, 2025
Stroke
is
a
leading
risk
factor
for
disability
and
death.
Necroptosis
involved
in
stroke
pathogenesis.
However,
the
molecular
mechanisms
underlying
necroptosis
remain
unclear.
The
mammalian
target
of
rapamycin
complex
1
(mTORC1)
modulates
gut
epithelium.
Eukaryotic
translation
initiation
4E
(eIF4E)-binding
protein-1
(4EPB1)
one
main
downstream
molecules
mTORC1.
This
study
addresses
role
4EBP1-eIF4E
pathway
necroptosis.
was
found
to
be
activated
both
necroptotic
HT-22
mouse
middle
cerebral
artery
occlusion
(MCAO)
models.
Functionally,
4EBP1
overexpression,
eIF4E
knockdown,
inhibition
suppressed
necroptosis,
respectively.
Furthermore,
positive
feedback
circuit
observed
between
receptor-interacting
protein-3
(RIP3)-mixed
lineage
kinase
domain-like
protein
(MLKL)
pathways,
which
RIP3-MLKL
activates
by
degrading
activating
eIF4E.
turn
enhanced
activation.
activation
derived
from
this
loop
may
stimulate
cytokine
production,
key
associated
with
Finally,
using
MCAO
model,
application
eIF4E,
RIP3,
MLKL
inhibitors
have
regulatory
mechanism
similar
that
vitro
study,
reducing
infarct
volume
improving
neurological
function
mice.
Cardiovascular Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 2, 2025
Abstract
Aims
Microvascular
endothelial
cells
dysfunction
can
significantly
worsen
ischaemic
stroke
outcomes
by
disrupting
tight
junctions
and
increasing
the
acquisition
of
adhesion
molecules,
accelerating
blood–brain
barrier
(BBB)
disruption
pro-inflammatory
response.
The
identification
drugs
that
improve
cell
function
may
be
crucial
for
stroke.
It
has
been
validated
empagliflozin
(EMPA),
a
novel
antidiabetic
drug,
protects
regardless
diabetic
status
patient.
However,
impact
EMPA
on
is
unclear.
We
hypothesized
would
exert
beneficial
effect
outcome
protecting
microvascular
against
junction
increase
molecules.
Methods
results
Young
adult
male
mice
were
administered
with
or
vehicle
(dimethyl
sulfoxide)
daily
7
days
before
being
subjected
to
transient
middle
cerebral
artery
occlusion
(tMCAO).
Neurological
deficits
evaluated
up
28
post-tMCAO.
Infarct
volume,
BBB
disruption,
inflammatory
assessed
1
day
after
tMCAO.bEnd.3
primary
brain
treated
under
oxygen
glucose
deprivation/reperfusion
(OGD/R),
lactate
dehydrogenase
release,
transendothelial
electrical
resistance,
leakage
fluorescein
isothiocyanate-dextran,
molecules
proteins
examined.
Mechanistic
studies
probing
conducted
RNA-seq.
treatment
ischaemia
markedly
improved
infarct
inflammation
1-day
post-tMCAO,
further
enhanced
neurobehavioral
days.
Pre-treatment
attenuated
OGD/R
conditions.
In
mechanistic
terms,
RNA-seq
data
from
isolated
microvessels
revealed
Wnt/β-catenin
signalling
pathway
was
preserved
in
group,
contrast
group.
inhibited
β-catenin
ubiquitination
promoted
translocation
cytoplasm
nucleus
function.
Importantly,
inhibitor
XAV-939
eliminated
this
protective
EMPA.
Conclusion
administration
tMCAO
ischaemia/reperfusion-induced
via
β-catenin-mediated
protection
cells.
Therefore,
shows
potential
improving
as
an
adjunctive
preventive
strategy.
