The cytosolic DNA‐sensing cGAS–STING pathway in neurodegenerative diseases
CNS Neuroscience & Therapeutics,
Год журнала:
2024,
Номер
30(3)
Опубликована: Март 1, 2024
Abstract
Background
With
the
widespread
prevalence
of
neurodegenerative
diseases
(NDs)
and
high
rates
mortality
disability,
it
is
imminent
to
find
accurate
targets
for
intervention.
There
growing
evidence
that
neuroimmunity
pivotal
in
pathology
NDs
interventions
targeting
hold
great
promise.
Exogenous
or
dislocated
nucleic
acids
activate
cytosolic
DNA
sensor
cyclic
GMP‐AMP
synthase
(cGAS),
activating
stimulator
interferon
genes
(STING).
The
activated
STING
triggers
innate
immune
responses
then
cGAS‐STING
signaling
pathway
links
abnormal
acid
sensing
response.
Recently,
numerous
studies
have
shown
neuroinflammation
regulated
by
plays
an
essential
role
NDs.
Aims
In
this
review,
we
summarized
mechanism
focused
on
inhibitors
cGAS‐STING.
Conclusion
important
pathogenesis
Inhibiting
may
provide
new
measures
treatment
Язык: Английский
The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer’s disease
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Март 4, 2025
The
relationship
between
Alzheimer's
disease
(AD)
and
neuroimmunity
has
gradually
begun
to
be
unveiled.
Emerging
evidence
indicates
that
cyclic
GMP-AMP
synthase
(cGAS)
acts
as
a
cytosolic
DNA
sensor,
recognizing
damage-associated
molecular
patterns
(DAMPs),
inducing
the
innate
immune
response
by
activating
stimulator
of
interferon
genes
(STING).
Dysregulation
this
pathway
culminates
in
AD-related
neuroinflammation
neurodegeneration.
A
substantial
body
mitochondria
are
involved
critical
pathogenic
mechanisms
AD,
whose
damage
leads
release
mitochondrial
(mtDNA)
into
extramitochondrial
space.
This
leaked
mtDNA
serves
DAMP,
various
pattern
recognition
receptors
defense
networks
brain,
including
cGAS-STING
pathway,
ultimately
leading
an
imbalance
homeostasis.
Therefore,
modulation
mtDNA-cGAS-STING
restore
neuroimmune
homeostasis
may
offer
promising
prospects
for
improving
AD
treatment
outcomes.
In
review,
we
focus
on
during
stress
activation
pathway.
Additionally,
delve
research
progress
further
discuss
primary
directions
potential
hurdles
developing
targeted
therapeutic
drugs,
gain
deeper
understanding
pathogenesis
provide
new
approaches
its
therapy.
Язык: Английский
STING immune activation of microglia aggravating neurovascular unit damage in diabetic retinopathy
Free Radical Biology and Medicine,
Год журнала:
2025,
Номер
233, С. 86 - 101
Опубликована: Март 30, 2025
Язык: Английский
Therapeutic targeting the cGAS−STING pathway associated with protein and gene: An emerging and promising novel strategy for aging-related neurodegenerative disease
International Immunopharmacology,
Год журнала:
2025,
Номер
156, С. 114679 - 114679
Опубликована: Апрель 18, 2025
Язык: Английский
cGAS/STING signalling pathway in senescence and oncogenesis
Seminars in Cancer Biology,
Год журнала:
2024,
Номер
106-107, С. 87 - 102
Опубликована: Авг. 31, 2024
Язык: Английский
The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases
Neurobiology of Disease,
Год журнала:
2024,
Номер
202, С. 106710 - 106710
Опубликована: Окт. 28, 2024
Neurodegenerative
diseases
(NDs)
are
a
type
of
common
chronic
progressive
disorders
characterized
by
damage
to
specific
cell
populations
in
the
nervous
system,
ultimately
leading
disability
or
death.
Effective
treatments
for
these
still
lacking,
due
limited
understanding
their
pathogeneses,
which
involve
multiple
cellular
and
molecular
pathways.
The
triggering
an
immune
response
is
feature
neurodegenerative
disorders.
A
critical
challenge
intricate
interplay
between
neuroinflammation,
neurodegeneration,
responses,
not
yet
fully
characterized.
In
recent
years,
cyclic
GMP-AMP
synthase
(cGAS)-stimulator
interferon
gene
(STING)
pathway,
crucial
intracellular
DNA
sensing,
has
gradually
gained
attention.
However,
roles
this
pathway
within
types
such
as
cells,
glial
neuronal
its
contribution
ND
pathogenesis,
remain
elucidated.
review,
we
systematically
explore
how
cGAS-STING
signaling
links
various
with
related
effector
pathways
under
context
NDs
multifaceted
therapeutic
directions.
We
emphasize
discovery
condition-dependent
heterogeneity
integral
diverse
responses
potential
targets.
Additionally,
review
pathogenic
role
activation
Parkinson's
disease,
ataxia-telangiectasia,
amyotrophic
lateral
sclerosis.
focus
on
complex
bidirectional
Alzheimer's
Huntington's
sclerosis,
revealing
double-edged
nature
disease
progression.
objective
elucidate
pivotal
pathogenesis
catalyze
new
insights
facilitating
development
novel
strategies.
Язык: Английский
Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal Angiogenesis
Asian Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
19(5), С. 100969 - 100969
Опубликована: Сен. 23, 2024
Retinal
neovascularization
is
a
leading
cause
of
blindness.
While
current
anti-VEGF
drugs
effectively
inhibit
pathological
angiogenesis,
some
patients
develop
resistance
or
reduced
responsiveness
to
treatments
over
time,
diminished
effectiveness.
In
this
study,
we
identified
high
activation
the
cGAS-STING
signaling
pathway,
which
exacerbated
and
vessel
leakage.
We
developed
an
injectable
thermo-responsive
supramolecular
hydrogel
loaded
with
anti-STING
drug.
The
hydrogel,
made
Pluronic
F127
(PF·127)
consisting
poly(ethylene
oxide)
poly(propylene
units,
demonstrated
excellent
transparency
biocompatibility.
Importantly,
thermo-sensitive
property
allowed
for
precise
spatial
release
drug,
extending
effective
treatment
duration
C-176,
suppressed
STING
in
retina,
inflammation,
protected
retinal
tissue.
Hydro
Язык: Английский
Activated Interferon Signaling Suppresses Age-Dependent Liver Cancer
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 3, 2024
Abstract
Age
is
a
major
risk
factor
for
liver
cancer,
as
the
case
most
adult
human
cancers.
However,
underlying
mechanisms
are
not
well
defined.
A
better
understanding
of
role
aging
in
and
other
cancers
can
facilitate
approaches
assessment,
early
detection
prevention.
We
hypothesize
that
age-driven
changes
render
aged
more
sensitive
to
oncogenic
stress
hence
tumorigenesis.
To
investigate
how
with
age,
we
documented
immune
profile,
transcriptome
epigenome
healthy
livers
from
both
young
mice,
revealing
pronounced
alterations
aging.
Notably,
hepatocytes,
identified
heightened
interferon
(IFN)
signaling,
simultaneous
tumor
suppressor
oncogene
signaling
at
bulk
single
cell
level,
suggestive
an
poised
neoplasia.
challenge
this
seemingly
state,
employed
adeno-associated
virus
(AAV)-mediated
expression
c-Myc
mouse
hepatocytes
vivo
.
Analysis
expressing
revealed
further
elevated
IFN
Stimulated
Genes
(ISGs).
This
ISG
upregulation
was
evident
multiple
models
transformation
older
mice
also
observed
humans
Metabolic
dysfunction-Associated
Steatohepatitis
(MASH).
determined
Stat1
necessary
sufficient
age
specific
old
wild
type
mice.
Remarkably,
inhibiting
Jak/Stat
alongside
ectopic
led
high-grade
hepatocyte
dysplasia
formation,
selectively
Together,
these
results
suggest
state
“precarious
balance”,
due
concurrent
activation
pathways,
but
protected
against
neoplastic
progression
by
IFN-signaling.
Age-dependent
has
been
many
tissues
recent
studies
have
demonstrated
its
detrimental
consequences
on
aging,
raising
question
why
IFN-signaling
activated
during
propose
intrinsically
higher
cancer
age-dependent
adaptive
process
protect
tumorigenesis,
one
maladaptive
consequences.
Язык: Английский
Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and Alzheimer’s disease by bioinformatics analysis and machine learning
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Авг. 27, 2024
Background
and
objectives
Periodontitis
(PD),
a
chronic
inflammatory
disease,
is
serious
threat
to
oral
health
one
of
the
risk
factors
for
Alzheimer’s
disease
(AD).
A
growing
body
evidence
suggests
that
two
diseases
are
closely
related.
However,
current
studies
have
not
provided
comprehensive
understanding
common
genes
mechanisms
between
PD
AD.
This
study
aimed
screen
crosstalk
AD
potential
relationship
cross-talk
PANoptosis-related
genes.
The
core
immune
cells
will
be
analyzed
provide
new
targets
clinical
treatment.
Materials
methods
datasets
were
downloaded
from
GEO
database
differential
expression
analysis
was
performed
obtain
DEGs.
Overlapping
DEGs
had
linking
OP,
obtained
literature
review.
Pearson
coefficients
used
compute
gene
correlations
in
datasets.
Cross-talk
intersection
AD-related
genes,
protein-protein
interaction(PPI)
networks
constructed
identified
using
STRING
database.
defined
as
cross-talk-PANoptosis
Core
screened
ROC
XGBoost.
PPI
subnetwork,
gene-biological
process,
gene-pathway
based
on
In
addition,
infiltration
CIBERSORT
algorithm.
Results
366
overlapping
with
109
XGBoost
showed
MLKL,
DCN,
IL1B,
IL18
more
accurate
than
other
predicting
well
better
overall
characterization.
GO
KEGG
analyses
four
involved
immunity
inflammation
organism.
Immune
B
naive,
Plasma
cells,
T
gamma
delta
significantly
differentially
expressed
patients
compared
normal
group.
Finally,
10
drugs
associated
retrieved
DGIDB
Conclusion
reveals
joint
mechanism
PANoptosis.
Analyzing
may
therapeutic
directions
pathogenesis
combined
Язык: Английский