bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 5, 2024
Abstract
Background
PANoptosis
is
an
integrated
form
of
cell
death
that
combines
features
pyroptosis,
apoptosis,
and
necroptosis
regulated
by
a
complex
network
signaling
proteins.
The
roles
ADAR1
(adenosine
deaminase
acting
on
RNA
1)
RIPK1
(receptor-interacting
serine/threonine-protein
kinase
in
orchestrating
the
ZBP1
(Z-DNA
binding
protein
1)-RIPK3
to
mediate
not
fully
understood,
particularly
context
heart
transplantation.
Objective
This
study
investigated
how
coordinate
activation
ZBP1-RIPK3
its
implications
mouse
Methods
Using
both
vitro
vivo
models,
we
analyzed
interactions
between
ADAR1,
RIPK1,
ZBP1,
RIPK3.
We
employed
western
blotting,
siRNA
elucidate
dynamics
these
interactions.
Additionally,
assessed
impact
transplantation
outcomes.
Results
Our
studies
revealed
regulates
for
PANoptosis.
interaction
with
protected
against
Z-DNA-induced
limiting
activations
In
study,
found
ligand
Z-DNA/Z-RNA
were
significantly
increased
graft
post-transplantation.
Furthermore,
deficiency
inhibited
cardiac
PANoptosis,
attenuated
acute
injury,
induced
long-term
survival.
Conclusion
elucidates
role
ZBP1-mediated
Inhibition
can
prevent
injury
rejection.
Understanding
mechanisms
provides
valuable
insights
into
regulation
may
inform
development
novel
therapeutic
strategies
improve
transplant
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 4, 2023
Abstract
Adult
neurogenic
decline,
inflammation,
and
neurodegeneration
are
phenotypic
hallmarks
of
Alzheimer’s
disease
(AD).
Mobilization
transposable
elements
(TEs)
in
heterochromatic
regions
was
recently
reported
AD,
but
the
underlying
mechanisms
still
underappreciated.
Combining
functional
genomics
with
differentiation
familial
sporadic
AD
patient
derived-iPSCs
into
hippocampal
progenitors,
CA3
neurons,
cerebral
organoids,
we
found
that
upregulation
AP-1
subunit,
c-Jun,
triggers
decondensation
genomic
containing
TEs.
This
leads
to
cytoplasmic
accumulation
HERVK-derived
RNA-DNA
hybrids,
activation
cGAS-STING
cascade,
increased
levels
cleaved
caspase-3,
suggesting
initiation
programmed
cell
death
progenitors
neurons.
Notably,
inhibiting
c-Jun
effectively
blocks
all
these
downstream
molecular
processes
rescues
neuronal
impaired
neurogenesis
phenotype
progenitors.
Our
findings
open
new
avenues
for
identifying
therapeutic
strategies
biomarkers
counteract
progression
diagnose
early,
pre-symptomatic
stages.
Cancer Biology and Medicine,
Год журнала:
2024,
Номер
unknown, С. 1 - 20
Опубликована: Янв. 3, 2024
The
intricate
interplay
between
the
human
immune
system
and
cancer
development
underscores
central
role
of
immunotherapy
in
treatment.
Within
this
landscape,
innate
system,
a
critical
sentinel
protecting
against
tumor
incursion,
is
key
player.
cyclic
GMP-AMP
synthase
(cGAS)
stimulator
interferon
genes
(STING)
pathway
has
been
found
to
be
linchpin
immunity:
activation
signaling
orchestrates
production
type
I
(IFN-α/β),
thus
fostering
maturation,
differentiation,
mobilization
effectors
microenvironment.
Furthermore,
STING
facilitates
release
presentation
antigens,
therefore
an
attractive
target
for
immunotherapy.
Current
strategies
activate
pathway,
including
use
pharmacological
agonists,
have
made
substantial
advancements,
particularly
when
combined
with
checkpoint
inhibitors.
These
approaches
shown
promise
preclinical
clinical
settings,
by
enhancing
patient
survival
rates.
This
review
describes
evolving
understanding
cGAS-STING
pathway’s
involvement
biology
therapy.
Moreover,
explores
classical
non-classical
providing
insights
into
their
mechanisms
action
potential
optimizing
strategies.
Despite
challenges
complexities,
promising
avenue
treatment
efficacy,
revolutionize
outcomes.
European journal of medical research,
Год журнала:
2025,
Номер
30(1)
Опубликована: Фев. 5, 2025
Acute
Osteofascial
Compartment
Syndrome
(AOCS)
stands
as
a
critical
surgical
emergency,
often
secondary
to
various
diseases.
Its
clinical
manifestation
arises
from
increased
pressure
within
the
fascial
compartment,
resulting
in
diminished
tissue
perfusion
and
consequential
ischemic
damage.
Presently,
diagnostics
lack
effective
biological
markers,
patients
face
grim
prognosis,
experiencing
muscle
contractures,
necrosis,
amputations,
renal
failure,
even
mortality.
The
primary
treatment,
fasciotomy,
poses
infection
risks
potential
nerve
Hence,
there
is
an
urgent
need
for
research
elucidating
AOCS's
pathogenic
mechanism
exploring
novel
treatments.
To
address
this,
we
established
rat
model
of
AOCS,
extracting
toe
flexor
muscles
both
experimental
control
groups.
Employing
second-generation
high-throughput
sequencing,
obtained
comprehensive
mRNA,
lncRNA,
circRNA,
miRNA
data.
Comparative
analysis
expression
differences
between
AOCS
groups,
followed
by
in-depth
examination,
allowed
us
unravel
intricacies
occurrence
multi-omics
perspective.
Our
findings
indicate
that
immune-mediated
inflammatory
disease,
primarily
involving
immune
cells,
especially
neutrophils.
In
addition,
genes
associated
with
ferroptosis,
form
regulated
cell
death,
are
found
be
upregulated
model,
non-coding
RNAs
playing
role
regulatory
interactions.
These
results
suggest
neutrophils
may
undergo
thereby
enhancing
inflammation
responses
which
promotes
disease
progression.
Furthermore,
these
reveal
interactions
molecules
pathways
significant
deeper
understanding
pathogenesis
development
targeted
therapeutic
strategies.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 7, 2025
This
paper
explored
the
novel
approach
of
targeting
cyclic
guanosine
monophosphate
(GMP)-adenosine
(AMP)
synthase-stimulator
interferon
genes
(cGAS-STING)
pathway
for
treatment
osteosarcoma
(OS).
Osteosarcoma
is
a
common
malignancy
in
adolescents.
Most
patients
die
from
lung
metastasis.
It
reviewed
epidemiology
and
pathological
characteristics
OS,
highlighting
its
highly
malignant
nature
tendency
pulmonary
metastasis,
underscoring
importance
identifying
new
therapeutic
targets.
The
cGAS-STING
was
closely
associated
with
biological
behaviors
OS
cells,
suggesting
that
this
could
be
promising
strategy.
Currently,
research
on
role
has
been
limited,
underlying
mechanisms
remain
unclear.
Therefore,
further
investigation
into
exploration
strategies
based
are
great
significance
developing
more
effective
treatments
OS.
offered
fresh
perspective
providing
hope
options
by
pathway.
Journal of the American Society of Nephrology,
Год журнала:
2024,
Номер
35(4), С. 466 - 482
Опубликована: Янв. 22, 2024
The
renal
immune
infiltrate
observed
in
autosomal
polycystic
kidney
disease
contributes
to
the
evolution
of
disease.
Elucidating
cellular
mechanisms
underlying
inflammatory
response
could
help
devise
new
therapeutic
strategies.
Here,
we
provide
evidence
for
a
mechanistic
link
between
deficiency
polycystin-1
and
mitochondrial
homeostasis
activation
cyclic
guanosine
monophosphate-adenosine
monophosphate
synthase
(cGAS)/stimulator
interferon
genes
(STING)
pathway.
Our
data
identify
cGAS
as
an
important
mediator
cystogenesis
suggest
that
its
inhibition
may
be
useful
slow
down
progression.
Disease Models & Mechanisms,
Год журнала:
2024,
Номер
17(4)
Опубликована: Апрель 1, 2024
ABSTRACT
Ankyrin
repeat
and
LEM
domain-containing
2
(ANKLE2)
is
a
scaffolding
protein
with
established
roles
in
cell
division
development,
the
dysfunction
of
which
increasingly
implicated
human
disease.
ANKLE2
regulates
nuclear
envelope
disassembly
at
onset
mitosis
its
reassembly
after
chromosome
segregation.
associated
abnormal
morphology
division.
It
by
mediating
protein-protein
interactions
barrier
to
autointegration
factor
(BANF1;
also
known
as
BAF)
kinase
phosphatase
that
modulate
phosphorylation
state
BAF.
In
brain
crucial
for
proper
asymmetric
neural
progenitor
cells.
humans,
pathogenic
loss-of-function
mutations
are
primary
congenital
microcephaly,
condition
not
properly
developed
birth.
linked
other
disease
pathologies,
including
Zika
syndrome,
cancer
tauopathy.
Here,
we
review
molecular
recent
literature
on
diseases
caused
dysfunction.
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.
