Gasdermins
oligomerize
to
form
pores
in
the
cell
membrane,
causing
regulated
lytic
death
called
pyroptosis.
Mammals
encode
five
gasdermins
that
can
trigger
pyroptosis:
GSDMA,
B,
C,
D,
and
E.
Caspase
granzyme
proteases
cleave
linker
regions
of
activate
GSDMB,
E,
but
no
endogenous
activation
pathways
are
yet
known
for
GSDMA.
Here,
we
perform
a
comprehensive
evolutionary
analysis
gasdermin
family.
A
gene
duplication
GSDMA
common
ancestor
caecilian
amphibians,
reptiles,
birds
gave
rise
GSDMA–D
mammals.
Uniquely
our
tree,
amphibian,
reptile,
bird
group
separate
clade
than
mammal
Remarkably,
numerous
species
contain
caspase-1
cleavage
sites
like
YVAD
or
FASD
linker.
We
show
from
birds,
reptiles
all
cleaved
by
caspase-1.
Thus,
was
originally
host-encoded
protease
In
mammals
site
is
disrupted;
instead,
new
protein,
GSDMD,
target
Mammal
uses
exosite
interactions
with
GSDMD
C-terminal
domain
confer
specificity
this
interaction,
whereas
stereotypical
tetrapeptide
sequence
Our
results
reveal
an
evolutionarily
stable
association
between
family,
albeit
shifting
one.
Caspase-1
repeatedly
changes
its
over
time
at
speciation
junctures,
initially
cleaving
GSDME
fish,
then
amphibians/reptiles/birds,
finally
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 10, 2025
Abstract
Staphylococcus
aureus
(
S.
)
is
a
major
zoonotic
pathogen,
with
mammary
gland
infections
contributing
to
mastitis,
condition
that
poses
significant
health
risks
lactating
women
and
adversely
affects
the
dairy
industry.
Therefore,
understanding
immune
mechanisms
underlying
caused
by
essential
for
developing
targeted
therapeutic
strategies
against
mastitis.
This
study
identified
hydroxycarboxylic
acid
receptor
2
(HCAR2)
as
potential
regulator
of
infection
in
glands.
It
demonstrated
HCAR2
deficiency
exacerbates
inflammatory
response
disrupts
blood‐milk
barrier
during
infection,
NLRP3
inflammasome‐mediated
pyroptosis
playing
central
role.
Activation
HCAR2,
on
other
hand,
suppressed
CMPK2
expression,
thereby
mitigating
mitochondrial
damage
mouse
epithelial
cells
(mMECs)
induced
.
Additionally,
DNA
(mtDNA)
released
from
‐infected
mMECs
activates
cGAS/STING
signaling
pathway
macrophages,
impairing
their
bactericidal
activity.
In
conclusion,
this
highlights
critical
role
provides
theoretical
basis
identifying
targets
such
infections.
Immunological Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 15, 2024
Macrophages,
neutrophils,
and
epithelial
cells
are
pivotal
components
of
the
host's
immune
response
against
bacterial
infections.
These
employ
inflammasomes
to
detect
various
microbial
stimuli
during
infection,
triggering
an
inflammatory
aimed
at
eradicating
pathogens.
Among
these
responses,
pyroptosis,
a
lytic
form
cell
death,
plays
crucial
role
in
eliminating
replicating
bacteria
recruiting
combat
invading
pathogen.
The
immunological
function
pyroptosis
varies
across
macrophages,
cells,
aligning
with
their
specific
roles
within
innate
system.
This
review
centers
on
elucidating
resisting
gram-negative
infections,
particular
focus
mechanisms
play
intestinal
cells.
Additionally,
we
underscore
type-specific
vivo
contexts
defense.
Gasdermins
oligomerize
to
form
pores
in
the
cell
membrane,
causing
regulated
lytic
death
called
pyroptosis.
Mammals
encode
five
gasdermins
that
can
trigger
pyroptosis:
GSDMA,
B,
C,
D,
and
E.
Caspase
granzyme
proteases
cleave
linker
regions
of
activate
GSDMB,
E,
but
no
endogenous
activation
pathways
are
yet
known
for
GSDMA.
Here,
we
perform
a
comprehensive
evolutionary
analysis
gasdermin
family.
A
gene
duplication
GSDMA
common
ancestor
caecilian
amphibians,
reptiles,
birds
gave
rise
GSDMA–D
mammals.
Uniquely
our
tree,
amphibian,
reptile,
bird
group
separate
clade
than
mammal
Remarkably,
numerous
species
contain
caspase-1
cleavage
sites
like
YVAD
or
FASD
linker.
We
show
from
birds,
reptiles
all
cleaved
by
caspase-1.
Thus,
was
originally
host-encoded
protease
In
mammals
site
is
disrupted;
instead,
new
protein,
GSDMD,
target
Mammal
uses
exosite
interactions
with
GSDMD
C-terminal
domain
confer
specificity
this
interaction,
whereas
stereotypical
tetrapeptide
sequence
Our
results
reveal
an
evolutionarily
stable
association
between
family,
albeit
shifting
one.
Caspase-1
repeatedly
changes
its
over
time
at
speciation
junctures,
initially
cleaving
GSDME
fish,
then
amphibians/reptiles/birds,
finally
Biomedicine & Pharmacotherapy,
Journal Year:
2023,
Volume and Issue:
170, P. 116001 - 116001
Published: Dec. 20, 2023
Intervertebral
disc
degeneration
(IVDD)
is
a
main
cause
of
low
back
pain
(LBP),
which
can
lead
to
disability
and
thus
generate
heavy
burden
on
society.
IVDD
characterized
by
decrease
in
nucleus
pulposus
cells
(NPCs)
endogenous
mesenchymal
stem
(MSCs),
degradation
the
extracellular
matrix,
macrophage
infiltration,
blood
vessel
nerve
ingrowth.
To
date,
therapeutic
approaches
regarding
mainly
include
conservative
treatment
surgical
intervention.
However,
both
only
relieve
symptoms
rather
than
stop
or
revert
progression
IVDD,
since
pathogenesis
not
yet
clear.
Pyroptosis,
Caspase
family
dependence
conducted
Gasdermin
family,
newly
discovered
mode
programmed
cell
death.
Pyroptosis
has
been
observed
NPCs,
annulus
fibrosus
(AFCs),
chondrocytes,
MSCs,
macrophages,
vascular
endothelial
neurons
may
contribute
IVDD.
MSCs
are
kind
pluripotent
that
be
found
almost
all
tissues.
have
strong
ability
secrete
vesicles
(EVs),
contain
exosomes,
microvesicles
apoptotic
bodies.
EVs
derived
from
play
an
important
role
pyroptosis
regulation
could
beneficial
for
alleviating
This
review
focuses
clarifying
improve
MSCs.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Oct. 23, 2024
The
genus
Salmonella
contains
the
most
common
foodborne
pathogens
frequently
isolated
from
food-producing
animals
and
is
responsible
for
zoonotic
infections
in
humans
animals.
infection
can
cause
intestinal
damage,
resulting
inflammation
disruption
of
homeostasis
more
severe
cases
lead
to
bacteremia.
Pyroptosis,
a
proinflammatory
form
programmed
cell
death,
involved
many
disease
processes.
Inflammasomes,
pyroptosis,
along
with
their
respective
signaling
cascades,
are
instrumental
preservation
homeostasis.
In
recent
years,
in-depth
study
our
comprehension
virulence
factors
effector
proteins
has
reached
an
extensive
level,
deficit
persists
knowledge
regarding
intrinsic
pathogenic
mechanisms
about
necessitating
continued
pursuit
understanding
investigation.
this
review,
we
discuss
occurrence
pyroptosis
induced
by
effectors
provide
new
ideas
elucidating
regulatory
through
which
trigger
could
pave
way
novel
concepts
strategies
clinical
prevention
treatment
associated
diseases.
PLoS Pathogens,
Journal Year:
2025,
Volume and Issue:
21(1), P. e1012884 - e1012884
Published: Jan. 30, 2025
Virulent
microbes
produce
proteins
that
interact
with
host
cell
targets
to
promote
pathogenesis.
For
example,
virulent
bacterial
pathogens
have
called
effectors
are
typically
enzymes
and
secreted
into
cells.
To
detect
respond
the
activities
of
effectors,
diverse
phyla
organisms
evolved
effector-triggered
immunity
(ETI).
In
ETI,
often
sensed
indirectly
by
detection
their
virulence
in
ETI
mechanisms
can
be
complex
involve
several
classes
proteins.
Guards
monitor
functional
or
physical
integrity
another
protein,
guardee
decoy,
become
activated
initiate
an
immune
response
when
decoy
is
modified
disrupted
effector.
A
has
intrinsic
anti-pathogen
function
intended
target
structurally
mimics
a
protein
activity
unintentionally
targeted
individual
domain
integrated
guard.
Here,
we
review
origins
focus
on
5
mechanisms,
which
key
steps
pathway
include
activation
caspase
RIPoptosome
inflammasome,
formation
pores
plasma
membrane,
release
cytokines
ending
death
pyroptosis.
Survey
been
shown
protective
mouse
models
infection,
reveal
how
distinct
regulators
inflammasome
pathways
act
as
guards
decoys
trigger
ETI.
Common
themes
highlighted
limited
mechanistic
understanding
bactericidal
discussed.
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 24, 2025
As
a
highly
prevalent
gastrointestinal
malignant
tumor,
colorectal
cancer
poses
serious
challenge
in
terms
of
increasing
morbidity
and
mortality
late
diagnosis
due
to
the
invisibility
disease.
Although
existing
therapies
are
diverse
but
limited
efficacy,
mechanism
programmed
cell
death
(PCD)
has
become
focus
research
its
central
role
maintaining
body
homeostasis
regulating
tumor
progression.
Multimodal
pathways,
such
as
apoptosis,
autophagy,
pyroptosis
ferroptosis,
have
shown
unique
advantages
inhibiting
proliferation
migration
cells
enhancing
sensitivity
chemotherapy
by
responding
internal
external
environmental
stimuli.
In
recent
years,
natural
products
risen
prominence
virtue
their
multi-target
synergistic
effects
chemo-sensitizing
properties,
opened
up
new
direction
for
treatment
precisely
PCD
pathway.
this
paper,
we
searched
PubMed,
Web
Science
CNKI
databases
relevant
studies
last
10
years
using
keywords
(Colorectal
cancer)
(programmed
death)
products.
This
work
retrieved
59
(55
from
past
5
4
years)
reveal
action
targeting
PCD,
aiming
provide
theoretical
support
practical
guidance
optimization
clinical
therapeutic
strategies
development
innovative
drugs.
Genome Biology and Evolution,
Journal Year:
2024,
Volume and Issue:
16(7)
Published: July 1, 2024
Abstract
Inflammasomes
are
multiprotein
complexes
that
form
in
response
to
ligands
originating
from
pathogens
as
well
alterations
of
normal
cell
physiology
caused
by
infection
or
tissue
damage.
These
structures
engage
a
robust
inflammatory
immune
eradicates
environmental
microbes
before
they
cause
disease,
and
slow
the
growth
bona
fide
pathogens.
Despite
their
undeniable
utility
immunity,
inflammasomes
radically
reduced
birds.
Perhaps
most
surprising
is
that,
within
all
birds,
NLRP3
retained,
while
its
signaling
adapter
ASC
lost,
suggesting
signals
via
novel
unknown
adapter.
Crocodilian
reptiles
turtles,
which
share
more
recent
common
ancestor
with
retain
many
lost
inflammasome
components,
indicating
deletion
occurred
after
birds
diverged
crocodiles.
Some
bird
lineages
have
even
extensive
loss,
songbirds
continuing
pare
down
until
only
CARD8
remain.
Remarkably,
caspase-1
but
downstream
targets
caspase-1:
IL-1β,
IL-18,
YVAD-linker
encoding
gasdermin
A.
This
suggests
can
signal
through
alternative
proteases
activate
cytokine
maturation
pyroptosis
songbirds.
observations
may
reveal
new
contexts
activation
be
relevant
mammalian
suggest
avenues
research
uncover
enigmatic
nature
poorly
understood
inflammasome.
ACS Materials Letters,
Journal Year:
2024,
Volume and Issue:
6(9), P. 4209 - 4229
Published: Aug. 19, 2024
Programmed
cell
death
(PCD)
is
crucial
for
renewal,
embryogenesis,
the
immune
response,
tissue
growth
regulation,
and
other
essential
biological
processes.
Recent
evidence
underscores
potential
of
harnessing
PCD
to
combat
bacterial
infections,
particularly
in
eradicating
antibiotic-resistant
superbugs.
Extensive
efforts
have
been
devoted
developing
PCD-mediated
anti-infective
agents
by
drawing
insights
from
materials
science,
chemistry,
immunology,
microbiology.
In
this
review,
challenges
addressing
infections
PCD-based
approaches
revolutionize
treatment
are
first
summarized
discussed.
Then,
a
comprehensive
examination
nanoantibacterial
therapy,
encompassing
various
pathways,
such
as
apoptosis,
ferroptosis,
cuproptosis,
immunogenic
death,
NETosis,
autophagy,
pyroptosis,
provided.
Finally,
barriers
prospects
PCD-driven
antimicrobial
strategies
explored.
