Liver International,
Journal Year:
2025,
Volume and Issue:
45(4)
Published: March 21, 2025
PANoptosis
is
a
multimodal
form
of
cell
death
that
involves
inflammatory,
apoptotic,
and
necroptotic
pathways,
playing
key
role
in
the
development
liver
diseases.
This
article
first
outlines
definition
characteristics
PANoptosis,
then
explores
its
mechanisms
action
different
types
diseases,
including
acute
injury,
failure,
metabolic
dysfunction-associated
fatty
disease,
hepatocellular
carcinoma.
Furthermore,
this
analyses
molecular
regulatory
network
potential
therapeutic
targets.
Finally,
summarises
current
research
on
diseases
future
directions,
it
reviews
emerging
mechanism
Cell,
Journal Year:
2024,
Volume and Issue:
187(15), P. 4061 - 4077.e17
Published: June 14, 2024
NLRs
constitute
a
large,
highly
conserved
family
of
cytosolic
pattern
recognition
receptors
that
are
central
to
health
and
disease,
making
them
key
therapeutic
targets.
NLRC5
is
an
enigmatic
NLR
with
mutations
associated
inflammatory
infectious
diseases,
but
little
known
about
its
function
as
innate
immune
sensor
cell
death
regulator.
Therefore,
we
screened
for
NLRC5's
role
in
response
infections,
PAMPs,
DAMPs,
cytokines.
We
identified
acts
drive
death,
PANoptosis,
specific
ligands,
including
PAMP/heme
heme/cytokine
combinations.
interacted
NLRP12
PANoptosome
components
form
complex,
suggesting
network
forms
similar
those
plants.
Mechanistically,
TLR
signaling
NAD+
levels
regulated
expression
ROS
production
control
death.
Furthermore,
NLRC5-deficient
mice
were
protected
hemolytic
models,
could
be
potential
target.
Immunological Reviews,
Journal Year:
2025,
Volume and Issue:
329(1)
Published: Jan. 1, 2025
ABSTRACT
Inflammasomes
are
crucial
mediators
of
both
antimicrobial
host
defense
and
inflammatory
pathology,
requiring
stringent
regulation
at
multiple
levels.
This
review
explores
the
pivotal
role
mitogen‐activated
protein
kinase
(MAPK)
signaling
in
modulating
inflammasome
activation
through
various
regulatory
mechanisms.
We
detail
recent
advances
understanding
MAPK‐mediated
NLRP3
priming,
licensing
activation,
with
emphasis
on
MAPK‐induced
activator
protein‐1
(AP‐1)
ERK1
JNK
licensing,
TAK1
connecting
death
receptor
to
activation.
Furthermore,
we
discuss
novel
insights
into
MAPK
human
NLRP1
focusing
MAP3K
member
ZAKα
as
a
key
linking
ribosomal
stress
Lastly,
work
elucidating
how
Bacillus
anthracis
lethal
toxin
(LeTx)
manipulates
induce
macrophage
apoptosis
an
immune
evasion
strategy,
counteraction
this
effect
genotype‐specific
Nlrp1b
certain
rodent
strains.
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(45)
Published: Nov. 6, 2024
NRCs
are
essential
helper
NLR
(nucleotide-binding
domain
and
leucine-rich
repeat)
proteins
that
execute
immune
responses
triggered
by
sensor
NLRs.
The
resting
state
of
NbNRC2
was
recently
shown
to
be
a
homodimer,
but
the
sensor-activated
remains
unclear.
Using
cryo-EM,
we
determined
structure
NbNRC2,
which
forms
hexameric
inflammasome-like
resistosome.
Mutagenesis
oligomerization
interface
abolished
signaling,
confirming
functional
significance
Comparative
structural
analyses
between
homodimer
homohexamer
revealed
substantial
rearrangements,
providing
insights
into
activation
mechanisms.
Furthermore,
comparisons
hexamer
previously
reported
CC-NLR
pentameric
assemblies
features
allowing
an
additional
protomer
integration.
structure,
assessed
released
AlphaFold
3
for
predicting
activated
oligomers,
revealing
high-confidence
modeling
other
amino-terminal
α1
helices,
region
proven
difficult
resolve
structurally.
Overall,
our
work
sheds
light
on
mechanisms
expands
understanding
diversity.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 19, 2024
Abstract
NRCs
are
essential
helper
NLR
(nucleotide-binding
domain
and
leucine-rich
repeat)
proteins
that
execute
the
immune
response
triggered
by
disease
resistance
proteins,
also
known
as
sensor
NLRs.
The
structure
of
resting
state
NbNRC2
was
recently
revealed
to
be
a
homodimer.
However,
sensor-activated
has
not
yet
been
elucidated.
In
this
study,
we
used
cryo-EM
determine
NbNRC2,
which
forms
hexameric
inflammasome-like
resistosome.
To
confirm
functional
significance
hexamer,
mutagenized
interfaces
involved
in
oligomerization
found
mutations
three
nucleotide-binding
interface
residues
abolish
signalling.
Comparative
structural
analyses
between
homodimer
homohexamer
significant
rearrangements
before
after
activation,
providing
insights
into
activation
mechanisms.
Furthermore,
comparisons
hexamer
previously
reported
CC-NLR
pentameric
assemblies
features
allow
for
integration
an
additional
protomer.
We
assess
released
AlphaFold
3
prediction
activated
oligomers.
This
allows
high-confidence
modelling
N-terminal
α
1-helices
other
CC-NLRs,
region
proven
difficult
fully
resolve
using
approaches.
Overall,
our
work
sheds
light
on
biochemical
mechanisms
underpinning
expands
understanding
diversity.
Journal of Innate Immunity,
Journal Year:
2024,
Volume and Issue:
16(1), P. 295 - 323
Published: Jan. 1, 2024
Evolutionarily,
immune
response
is
a
complex
mechanism
that
protects
the
host
from
internal
and
external
threats.
Pattern-recognition
receptors
(PRRs)
recognize
MAMPs,
PAMPs,
DAMPs
to
initiate
protective
pro-inflammatory
response.
PRRs
are
expressed
on
cell
membranes
by
TLR1,
2,
4,
6
in
cytosolic
organelles
TLR3,
7,
8,
9,
NLRs,
ALRs,
cGLRs.
We
know
their
downstream
signaling
pathways
controlling
immunoregulatory
However,
impact
of
metabolic
control
cells
pro-
anti-inflammatory
activity
has
not
been
discussed
extensively.
