Regulation and Function of the cGAS-STING Pathway: Mechanisms, Post-Translational Modifications, and Therapeutic Potential in Immunotherapy
Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 1721 - 1739
Опубликована: Март 1, 2025
Abstract:
Autoimmune
diseases
arise
when
the
immune
system
attacks
healthy
tissues,
losing
tolerance
for
self-tissues.
Normally,
recognizes
and
defends
against
pathogens
like
bacteria
viruses.
The
cGAS-STING
pathway,
activated
by
pattern-recognition
receptors
(PRRs),
plays
a
key
role
in
autoimmune
responses.
cGAS
protein
senses
pathogenic
DNA
synthesizes
cGAMP,
which
induces
conformational
changes
STING,
activating
kinases
IKK
TBK1
leading
to
expression
of
interferon
genes
or
inflammatory
mediators.
This
pathway
is
crucial
immunotherapy,
innate
immunity,
enhancing
antigen
presentation,
modulating
tumor
microenvironment,
integrating
into
therapeutic
strategies.
Modulation
strategies
include
small
molecule
inhibitors,
oligonucleotide
therapies,
antibody
genetic
epigenetic
regulation,
cytokine
metabolite
modulation,
nanoscale
delivery
systems.
Post-translational
modifications
(PTMs)
such
as
phosphorylation,
acetylation,
ubiquitination,
methylation,
palmitoylation,
glycosylation,
fine-tune
responses
regulating
activity,
stability,
localization,
interactions.
These
are
interconnected
collectively
influence
functionality.
We
summarize
functions
its
PTMs
non-immune
cells
across
various
diseases,
explore
potential
clinical
applications.
Keywords:
cGAS,
post-transcriptional
regulation
Язык: Английский
Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 7411 - 7411
Опубликована: Июль 5, 2024
Advancing
age
is
associated
with
several
age-related
diseases
(ARDs),
musculoskeletal
conditions
impacting
millions
of
elderly
people
worldwide.
With
orthopedic
contributing
towards
considerable
number
patients,
a
deeper
understanding
bone
aging
the
need
hour.
One
underlying
factors
cellular
senescence
and
its
secretory
phenotype
(SASP).
SASP
comprises
pro-inflammatory
markers,
cytokines
chemokines
that
arrest
cell
growth
development.
The
accumulation
over
years
leads
to
chronic
low-grade
inflammation
advancing
age,
also
known
as
inflammaging.
pathways
molecular
mechanisms
focused
on
inflammaging
are
currently
limited
but
increasingly
being
explored.
Most
genes,
involved
in
coincide
those
cancer
other
ARDs
like
osteoarthritis
(OA).
Thus,
exploring
these
using
techniques
sequencing,
identifying
combatting
them
most
suitable
approach
crucial
for
healthy
early
detection
ARDs.
Several
approaches
can
be
used
aid
regeneration
reduce
bone.
These
may
pharmacological,
non-pharmacological
lifestyle
interventions.
increasing
evidence
intricate
relationship
between
aging,
senescence,
ARDs,
anti-aging
strategies
marrow
(BM).
Язык: Английский
Nature of the Association between Rheumatoid Arthritis and Cervical Cancer and Its Potential Therapeutic Implications
Nutrients,
Год журнала:
2024,
Номер
16(15), С. 2569 - 2569
Опубликована: Авг. 5, 2024
It
is
now
established
that
patients
with
rheumatoid
arthritis
(RA)
have
an
increased
risk
of
developing
cervical
cancer
(CC)
or
its
precursor,
intraepithelial
neoplasia
(CIN).
However,
the
underlying
mechanisms
this
association
not
been
elucidated.
RA
characterized
by
unresolved
chronic
inflammation.
suggested
human
papillomavirus
(HPV)
infection
in
exacerbates
inflammation,
increasing
CC.
The
tumor
microenvironment
CC
also
marked
which
aggravates
manifestations
both
conditions.
Gut
and
vaginal
dysbiosis
are
considered
potential
contribute
to
inflammation
aggravation
manifestations.
Numerous
clinical
pre-clinical
studies
demonstrated
beneficial
effects
various
nutritional
approaches
attenuate
including
polyunsaturated
fatty
acids
their
derivatives,
specialized
pro-resolving
mediators
(SPMs),
probiotics,
prebiotics,
certain
diets.
We
believe
successful
resolution
correction
dysbiosis,
combination
current
anti-RA
anti-CC
therapies,
a
promising
therapeutic
approach
for
This
could
reduce
development
HPV-infected
patients.
Язык: Английский
A central role of stimulator of interferon genes’ adaptor protein in defensive immune response
Immunologic Research,
Год журнала:
2025,
Номер
73(1)
Опубликована: Янв. 21, 2025
Язык: Английский
Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis
Journal of Translational Autoimmunity,
Год журнала:
2025,
Номер
unknown, С. 100284 - 100284
Опубликована: Март 1, 2025
Язык: Английский
Development of indole derivatives as inhibitors targeting STING-dependent inflammation
Bioorganic & Medicinal Chemistry,
Год журнала:
2025,
Номер
126, С. 118216 - 118216
Опубликована: Апрель 27, 2025
Язык: Английский
Impact of Microplastics on Human Health: Risks, Diseases, and Affected Body Systems
Microplastics,
Год журнала:
2025,
Номер
4(2), С. 23 - 23
Опубликована: Май 7, 2025
This
review
article
aims
to
highlight
the
potential
harm
caused
by
microplastics
(MPs)
in
different
organs
and
systems
underscore
need
for
further
investigation
into
their
action
mechanisms.
MPs,
such
as
polystyrene,
polypropylene,
polyethylene,
significantly
impact
human
health,
causing
inflammation
respiratory
gastrointestinal
systems,
compromising
immune
function,
increasing
risk
of
cardiovascular
diseases
neurotoxicity.
These
effects
are
largely
attributed
role
MPs
disrupting
hormonal
regulation,
which
can
lead
reproductive
disorders
an
elevated
cancer.
microscopic
particles
(less
than
5
mm
size)
now
ubiquitous
air,
water,
food.
However,
much
existing
research
on
focuses
mechanisms
association
with
health
disease,
limited
emphasis
direct
humans
or
long-term
consequences.
To
effectively
address
plastic
toxicity,
it
is
crucial
understand
policy
implications
relevance
disease
development.
Recent
has
highlighted
more
stringent
regulatory
oversight
these
materials
better
mitigate
health.
Язык: Английский
Inhibition of histone deacetylases 3 attenuates imiquimod-induced psoriatic dermatitis via targeting cGAS-STING signaling in keratinocytes
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Июнь 2, 2025
Psoriasis
is
a
common
chronic
inflammatory
skin
disease
characterized
by
epidermal
keratinocyte
hyperproliferation
and
persistent
immune
activation.
Histone
deacetylase
3
(HDAC3),
member
of
the
class
I
HDAC
family,
plays
critical
roles
in
regulating
immunity
inflammation.
However,
its
precise
expression
profile
functional
contribution
to
psoriasis
pathogenesis
remain
poorly
defined.
We
first
performed
bioinformatics
analysis
HDAC3
using
Gene
Expression
Omnibus
(GEO)
database.
Subsequently,
we
employed
combination
cellular
molecular
techniques,
including
hematoxylin
eosin
(H&E)
staining,
immunohistochemistry,
flow
cytometry,
quantitative
real-time
PCR
(qRT-PCR),
western
blotting,
transmission
electron
microscopy
(TEM),
analyze
role
IMQ-induced
psoriasis-like
inflammation
mice
vitro
models.
was
significantly
upregulated
lesions
patients
both
vivo
models
psoriasis.
Pharmacological
inhibition
specific
inhibitor
RGFP966
alleviated
suppressed
phenotypes
vitro.
Mechanistically,
upregulation
an
microenvironment
promoted
oxidative
stress,
disrupted
mitochondrial
structural
integrity,
triggered
DNA
leakage
into
cytosol,
thereby
activating
cGAS-STING
pathway
keratinocytes.
Our
findings
establish
as
pivotal
mediator
through
via
dysfunction.
The
exacerbating
highlights
potential
therapeutic
target.
Targeting
keratinocytes
may
offer
novel
strategy
for
preventing
treating
modulating
epigenetic
regulation,
homeostasis,
innate
responses.
Язык: Английский
The cross-talk between the cGAS-STING signaling pathway and chronic inflammation in the development of musculoskeletal disorders
Ageing Research Reviews,
Год журнала:
2024,
Номер
unknown, С. 102602 - 102602
Опубликована: Ноя. 1, 2024
Язык: Английский
Review of Excessive Cytosolic DNA and Its Role in AIM2 and cGAS-STING Mediated Psoriasis Development
Clinical Cosmetic and Investigational Dermatology,
Год журнала:
2024,
Номер
Volume 17, С. 2345 - 2357
Опубликована: Окт. 1, 2024
In
psoriasis,
keratinocytes
are
triggered
by
factors,
such
as
infection
or
tissue
damage,
to
release
DNA,
which
thereby
activates
plasmacytoid
dendritic
cells
and
macrophages
induce
inflammation,
thickened
epidermis,
parakeratosis.
The
recognition
of
double-stranded
(ds)DNA
facilitates
the
activation
cytoplasmic
DNA
sensors
absent
in
melanoma
2
(AIM2)
inflammasome
assembly
cyclic
guanosine
monophosphate
adenosine
(cGAMP)
synthase
(cGAS)
-
stimulator
interferon
gene
(STING)
pathway,
both
play
a
pivotal
role
mediating
inflammatory
response
driving
progression
psoriasis.
Additionally,
secreted
proinflammatory
cytokines
can
stimulate
further
from
keratinocytes.
Notably,
AIM2
cGAS-STING
signaling
pathways
also
mediates
programmed
cell
death,
potentially
enhancing
overproduction.
As
result,
excessive
activate
these
pathways,
amplifying
persistent
responses
that
contribute
maintenance
Several
studies
have
validated
targeting
its
mediated
offers
promising
therapeutic
strategies
for
Here,
we
postulate
hypothesis
cytosolic
cGAS-STING,
inflammation
ultimately
fostering
accumulation
contributing
development
Язык: Английский