Journal of Alzheimer s Disease,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 28, 2025
Background
Alzheimer's
disease
(AD)
causes
cognitive
function
disorder
and
has
become
the
preeminent
cause
of
dementia.
Glucagon-like
peptide-1
(GLP-1)
receptor
agonists,
semaglutide,
have
shown
positive
effects
on
promoting
function.
However,
research
about
mechanism
semaglutide
as
a
therapeutic
intervention
in
AD
is
sparse.
Objective
This
study
was
to
investigate
efficacy
transgenic
mouse
model
pathology
explored
detailed
by
modulated
neuroinflammatory
processes.
Methods
Male
amyloid
precursor
protein/presenilin
1
(APP/PS1)
mice
were
treated
with
or
vehicle
for
8
weeks.
Morris
water
maze
test
used
assess
recognition
Pathology
analysis
performed
detect
deposition
plaques.
High-throughput
sequencing
applied
specify
mechanism.
Microglia
astrocyte
activation
assessed
immunofluorescent
staining.
Inflammation
cytokine
levels
evaluated
enzyme-linked
immunosorbent
assay
(ELISA).
Related
proteins
pathway
western
blot.
Results
Semaglutide
treatment
attenuated
Aβ
accumulation
enhanced
APP/PS1
mice.
Through
transcriptomic
profiling,
immunohistochemical
staining,
ELISA,
substantiated
inhibit
overactivation
microglia
astrocytes,
well
curtail
secretion
inflammatory
mediators.
Furthermore,
robustly
activated
AMP-activated
protein
kinase
(AMPK)
suppressed
toll-like
4
(TLR4)/nuclear
factor-kappa
B
(NF-κB)
signaling
cascade,
thus
reducing
dampening
cascade.
Conclusions
The
results
demonstrated
that
mitigated
neuroinflammation
decelerated
advance
Biomedicines,
Год журнала:
2024,
Номер
12(8), С. 1737 - 1737
Опубликована: Авг. 2, 2024
Microglial
cells
exhibit
properties
akin
to
macrophages,
thereby
enabling
them
support
and
protect
the
central
nervous
system
environment.
Aging
induces
alterations
in
microglial
polarization,
resulting
a
shift
toward
neurotoxic
phenotype
characterized
by
increased
expression
of
pro-inflammatory
markers.
Dysregulation
cells'
regulatory
pathways
interactions
with
neurons
contribute
chronic
activation
neurodegeneration.
A
better
understanding
involvement
microglia
neurodegenerative
diseases
such
as
Alzheimer's
Parkinson's
is
critical
topic
for
studying
role
inflammatory
responses
disease
progression.
Furthermore,
metabolic
changes
aged
microglia,
including
downregulation
oxidative
phosphorylation,
are
discussed
this
review.
Understanding
these
mechanisms
crucial
developing
preventive
therapeutic
strategies.
Neurology Neuroimmunology & Neuroinflammation,
Год журнала:
2024,
Номер
11(4)
Опубликована: Май 29, 2024
New-onset
refractory
status
epilepticus
(NORSE)
occurs
in
previously
healthy
children
or
adults,
often
followed
by
epilepsy
and
poor
outcomes.
The
mechanisms
that
transform
a
normal
brain
into
an
epileptic
one
capable
of
seizing
for
prolonged
periods
despite
treatment
remain
unclear.
Nonetheless,
several
pieces
evidence
suggest
immune
dysregulation
could
contribute
to
hyperexcitability
modulate
NORSE
sequelae.
Sepsis-associated
encephalopathy
(SAE)
is
a
severe
and
frequent
septic
complication,
characterized
by
neuronal
damage
as
key
pathological
features.
The
astrocyte–microglia
crosstalk
in
the
central
nervous
system
(CNS)
plays
important
roles
various
neurological
diseases.
However,
how
astrocytes
interact
with
microglia
to
regulate
injury
SAE
poorly
defined.
In
this
study,
we
aim
investigate
molecular
basis
of
underlying
pathogenesis
also
explore
new
therapeutic
strategies
targeting
devastating
disease.
We
established
human
astrocyte/microglia
coculture
on
microfluidic
device,
which
allows
real-time
high-resolution
recording
glial
responses
inflammatory
stimuli.
Based
system,
can
test
lipopolysaccharide
(LPS)
treatment,
identify
cues
that
mediate
condition.
addition,
mouse
model
was
utilized
determine
state
cells
evaluate
effect
drugs
vivo.
Here,
found
activated
exhibited
close
spatial
interaction
model.
Upon
LPS
exposure
for
astrocytes,
detected
more
migrated
astrocyte
culture
compartment
accompanied
M1
polarization
increased
cell
motility
microglia.
Cytokine
array
analysis
revealed
less
interleukin
11
(IL11)
secreted
following
further
promoted
reprogramming
pro-inflammatory
phenotype
via
nuclear
factor-κB
(NF-κB)
signaling
pathway.
Intriguingly,
IL11
addition
markedly
rescued
LPS-induced
injuries
brain
This
study
defines
an
unknown
mediated
IL11,
contributed
neuropathogenesis
SAE,
suggested
potential
value
Medicinal Research Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 4, 2025
ABSTRACT
Astrocytes
undergo
a
reactive
transformation
in
central
nervous
system
(CNS)
disorders,
manifesting
significant
heterogeneity
morphology,
molecules,
function,
and
spatial
distribution.
Just
like
all
cells,
astrocytes
necessitate
energy
for
their
basic
functions.
Energy
production
proves
critical
the
survival
development
of
astrocytes,
as
well
fate
determination
functional
diversity.
The
activation
process
involves
metabolic
shift
energy,
yet
our
understanding
how
this
change
impacts
remains
limited.
In
comprehensive
review,
we
begin
by
outlining
advancements
research
on
CNS
establishing
crucial
association
between
metabolism
molecular
aspects.
Following
this,
delve
into
thorough
analysis
transitions
within
context
diseases.
Starting
from
essential
pathways
metabolism,
present
novel
perspective,
shedding
light
considering
metabolism.
conclusion,
propose
that
modulation
coupled
with
promotion
functionality
toward
disease
recovery,
represents
cutting‐edge
promising
strategy
treatment
