RNA
editing
is
a
posttranscriptional
mechanism
that
targets
changes
in
transcripts
to
modulate
innate
immune
responses.
We
report
the
role
of
astrocyte-specific,
ADAR1-mediated
neuroinflammation
Parkinson’s
disease
(PD).
generated
human
induced
pluripotent
stem
cell–derived
astrocytes,
neurons
and
cocultures
exposed
them
small
soluble
alpha-synuclein
aggregates.
Oligomeric
triggered
an
inflammatory
glial
state
associated
with
Toll-like
receptor
activation,
viral
responses,
cytokine
secretion.
This
reactive
resulted
loss
neurosupportive
functions
induction
neuronal
toxicity.
Notably,
interferon
response
pathways
were
activated
leading
up-regulation
isoform
switching
deaminase
enzyme,
ADAR1.
ADAR1
mediates
A-to-I
editing,
increases
observed
cells,
as
well
postmortem
PD
brain.
Aberrant,
or
dysregulated,
responses
may
lead
sustained
states
astrocytes
by
aggregation,
this
drive
neuroinflammatory
cascade
Parkinson’s.
Journal of Inflammation Research,
Год журнала:
2023,
Номер
Volume 16, С. 1523 - 1532
Опубликована: Апрель 1, 2023
Abstract:
PANoptosis
is
a
new
cell
death
proposed
by
Malireddi
et
al
in
2019,
which
characterized
pyroptosis,
apoptosis
and
necroptosis,
but
cannot
be
explained
any
of
them
alone.
The
interaction
between
necroptosis
involved
PANoptosis.
In
this
review,
from
the
perspective
PANoptosis,
we
focus
on
relationship
key
molecules
process
formation
PANoptosome,
as
well
role
diseases.
We
aim
to
understand
mechanism
provide
basis
for
targeted
intervention
PANoptosis-related
treat
human
Keywords:
apoptosis,
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Апрель 29, 2024
Abstract
Receptor-interacting
protein
kinase
3
(RIPK3),
a
member
of
the
receptor-interacting
(RIPK)
family
with
serine/threonine
activity,
interacts
RIPK1
to
generate
necrosomes,
which
trigger
caspase-independent
programmed
necrosis.
As
vital
component
RIPK3
plays
an
indispensable
role
in
necroptosis,
is
crucial
for
human
life
and
health.
In
addition,
participates
pathological
process
several
infections,
aseptic
inflammatory
diseases,
tumors
(including
tumor-promoting
-suppressive
activities)
by
regulating
autophagy,
cell
proliferation,
metabolism
production
chemokines/cytokines.
This
review
summarizes
recent
research
progress
regulators
signaling
pathway
discusses
potential
RIPK3/necroptosis
aetiopathogenesis
various
diseases.
An
in-depth
understanding
mechanisms
functions
may
facilitate
development
novel
therapeutic
strategies.
Experimental & Molecular Medicine,
Год журнала:
2023,
Номер
55(11), С. 2320 - 2331
Опубликована: Ноя. 9, 2023
Abstract
Nucleic
acid
sensing
is
involved
in
viral
infections,
immune
response-related
diseases,
and
therapeutics.
Based
on
the
composition
of
nucleic
acids,
sensors
are
defined
as
DNA
or
RNA
sensors.
Pathogen-associated
acids
recognized
by
membrane-bound
intracellular
receptors,
known
pattern
recognition
receptors
(PRRs),
which
induce
innate
immune-mediated
antiviral
responses.
PRR
activation
tightly
regulated
to
eliminate
infections
prevent
abnormal
excessive
an
essential
mechanism
tumor
immunotherapy
gene
therapies
that
target
cancer
infectious
diseases
through
genetically
engineered
cells
therapeutic
acids.
supports
priming
desirable
responses
during
treatment.
Recent
studies
have
shown
affects
efficiency
therapy
inhibiting
translation.
Suppression
immunity
induced
small-molecule
inhibitors,
virus-derived
proteins,
chemical
modifications
offers
a
potential
strategy.
Herein,
we
review
mechanisms
regulation
sensing,
specifically
covering
recent
advances.
Furthermore,
summarize
discuss
research
progress
regarding
different
effects
efficacy.
This
study
provides
insights
for
application
therapy.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115696 - 115696
Опубликована: Окт. 12, 2023
Programmed
cell
death
(PCD)
is
a
key
mechanism
for
the
study
of
anticancer
drugs
and
has
significant
impact
on
development
management
cancer.
A
growing
amount
data
indicates
that
different
kinds
PCD,
particularly
pyroptosis,
apoptosis,
necroptosis,
interact
closely.
Recent
research
revealed
existence
distinct
inflammatory
PCD
modality
known
as
PANoptosis,
which
controlled
by
complex
PANoptosome
complexes
built
combining
elements
from
pathways.
No
single
route
sufficient
to
explain
all
physiologic
effects
seen
in
PANoptosis.
Numerous
studies
have
demonstrated
PANoptosis
can
successfully
stop
cancer
cells
growing,
proliferating,
developing
drug
resistance.
As
result,
it
changed
focus
targeted
therapy.
In
this
review,
we
outlined
molecular
processes
activation
modulation
well
mechanisms
innate
immune
death.
order
provide
theoretical
foundation
targeting
an
anti-cancer
target,
also
highlight
PANoptosomes
discovered
date
give
overview
implications
treatment.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Янв. 25, 2024
Nucleic
acids
are
among
the
most
essential
PAMPs
(pathogen-associated
molecular
patterns).
Animals
have
evolved
numerous
sensors
to
recognize
nucleic
and
trigger
immune
signaling
against
pathogen
replication,
cellular
stress
cancer.
Many
sensor
proteins
(e.g.,
cGAS,
AIM2,
TLR9)
signature
of
infection
or
responsible
for
innate
response
DNA.
Remarkably,
recent
evidence
demonstrates
that
cGAS-like
receptors
acquire
ability
sense
RNA
in
some
forms
life.
Compared
with
nucleic-acid
sensing
by
responses
based
on
various
sensors,
including
RIG-I,
MDA5,
ADAR1,
TLR3/7/8,
OAS1,
PKR,
NLRP1/6,
ZBP1,
via
a
broad-spectrum
axis.
Importantly,
new
advances
brought
light
potential
clinical
application
targeting
these
pathways.
Here,
we
highlight
latest
discoveries
field.
We
also
summarize
activation
regulatory
mechanisms
RNA-sensing
signaling.
In
addition,
discuss
how
is
tightly
controlled
cells
why
disruption
homeostasis
linked
disease.
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 9, 2025
The
innate
immune
system
promptly
detects
and
responds
to
invading
pathogens,
with
a
key
role
played
by
the
recognition
of
bacterial-derived
DNA
through
pattern
receptors.
Z-DNA
binding
protein
1
(ZBP1)
functions
as
sensor
inducing
type
I
interferon
(IFN)
production,
responses
also
inflammatory
cell
death.
ZBP1
interacts
cytosolic
via
its
DNA-binding
domains,
crucial
for
activation.
Brucella
abortus
is
etiologic
agent
brucellosis
in
livestock
humans,
leading
significant
economic
losses
public
health
impact.
Despite
other
sensors
that
recognize
B.
DNA,
including
Toll-like
receptor
9
Stimulator
genes
(STING),
here
we
evaluated
participation
sensing
infection.
Using
macrophages
derived
from
knockout
(KO)
mice
demonstrated
partially
contributes
IFN-β
expression
upon
infection
or
transfection.
knockdown
STING
siRNA
decreased
residual
signal
elicited
infection,
demonstrating
presence
redundant
DNA-sensing
mechanism
driving
IFN
production.
Furthermore,
involved
signaling
IRF-1
expression.
Additionally,
Unfolded
Protein
Response
(UPR)
activation
during
However,
does
not
influence
production
proinflammatory
mediators,
inflammasome
it
dispensable
control
bacterial
replication
macrophages.
This
study
highlights
complex
interactions
components
receptors
identifies
DNA-induced
response.
Molecules,
Год журнала:
2022,
Номер
28(1), С. 52 - 52
Опубликована: Дек. 21, 2022
Cell
death
is
a
fundamental
pathophysiological
process
in
human
disease.
The
discovery
of
necroptosis,
form
regulated
necrosis
that
induced
by
the
activation
receptors
and
formation
necrosome,
represents
major
breakthrough
field
cell
past
decade.
Z-DNA-binding
protein
(ZBP1)
an
interferon
(IFN)-inducing
protein,
initially
reported
as
double-stranded
DNA
(dsDNA)
sensor,
which
induces
innate
inflammatory
response.
Recently,
ZBP1
was
identified
important
sensor
necroptosis
during
virus
infection.
It
connects
viral
nucleic
acid
receptor-interacting
kinase
3
(RIPK3)
via
two
domains
necrosome.
Recent
studies
have
also
non-viral
infections
mediates
necrotic
signal
transduction
unique
mechanism.
This
review
highlights
its
novel
findings
provides
insight
into
critical
role
crosstalk
between
different
types
death,
may
represent
new
therapeutic
option.
