The gasdermin family: emerging therapeutic targets in diseases
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Апрель 7, 2024
Abstract
The
gasdermin
(GSDM)
family
has
garnered
significant
attention
for
its
pivotal
role
in
immunity
and
disease
as
a
key
player
pyroptosis.
This
recently
characterized
class
of
pore-forming
effector
proteins
is
orchestrating
processes
such
membrane
permeabilization,
pyroptosis,
the
follow-up
inflammatory
response,
which
are
crucial
self-defense
mechanisms
against
irritants
infections.
GSDMs
have
been
implicated
range
diseases
including,
but
not
limited
to,
sepsis,
viral
infections,
cancer,
either
through
involvement
pyroptosis
or
independently
this
process.
regulation
GSDM-mediated
gaining
recognition
promising
therapeutic
strategy
treatment
various
diseases.
Current
strategies
inhibiting
GSDMD
primarily
involve
binding
to
GSDMD,
blocking
cleavage
GSDMD-N-terminal
(NT)
oligomerization,
albeit
with
some
off-target
effects.
In
review,
we
delve
into
cutting-edge
understanding
interplay
between
elucidate
activation
GSDMs,
explore
their
associations
diseases,
discuss
recent
advancements
potential
developing
inhibitors.
Язык: Английский
Gasdermins as evolutionarily conserved executors of inflammation and cell death
Nature Cell Biology,
Год журнала:
2024,
Номер
26(9), С. 1394 - 1406
Опубликована: Авг. 26, 2024
Язык: Английский
Mechanistic insights into gasdermin-mediated pyroptosis
Nature Reviews Molecular Cell Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
Язык: Английский
Harnessing Pyroptosis for Cancer Immunotherapy
Cells,
Год журнала:
2024,
Номер
13(4), С. 346 - 346
Опубликована: Фев. 16, 2024
Cancer
immunotherapy
is
a
novel
pillar
of
cancer
treatment
that
harnesses
the
immune
system
to
fight
tumors
and
generally
results
in
robust
antitumor
immunity.
Although
has
achieved
remarkable
clinical
success
for
some
patients,
many
patients
do
not
respond,
underscoring
need
develop
new
strategies
promote
Pyroptosis
an
immunostimulatory
type
regulated
cell
death
activates
innate
system.
A
hallmark
pyroptosis
release
intracellular
contents
such
as
cytokines,
alarmins,
chemokines
can
stimulate
adaptive
activation.
Recent
studies
suggest
promotes
Here,
we
review
mechanisms
by
which
be
induced
highlight
induce
cells
defense.
We
discuss
how
modulates
tumor
microenvironment
immunity
also
research
areas
focus
on
continued
development
anticancer
treatment.
Pyroptosis-based
therapies
offer
promising
avenue
treating
immunologically
'cold'
tumors.
Язык: Английский
Unanticipated Loss of Inflammasomes in Birds
Genome Biology and Evolution,
Год журнала:
2024,
Номер
16(7)
Опубликована: Июль 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.
Язык: Английский
Caspase 3 proteolytically inactivates gasdermin Ec and inhibits pyroptosis in an early vertebrate
Comparative Immunology Reports,
Год журнала:
2025,
Номер
unknown, С. 200216 - 200216
Опубликована: Март 1, 2025
Язык: Английский
Pyroptosis: molecular mechanisms and roles in disease
Cell Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
Язык: Английский
Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(10), С. 4195 - 4227
Опубликована: Июнь 28, 2024
Cell
death
is
a
central
process
for
organismal
health.
Pyroptosis,
namely
pyroptotic
cell
death,
recognized
as
critical
type
that
disrupts
membrane
and
triggers
pro-inflammatory
cytokine
secretion
Язык: Английский
Starvation-induced phosphorylation activates gasdermin A to initiate pyroptosis
Cell Reports,
Год журнала:
2024,
Номер
43(9), С. 114728 - 114728
Опубликована: Сен. 1, 2024
Pyroptosis,
a
pro-inflammatory
form
of
programmed
cell
death,
is
crucial
for
host
defense
against
pathogens
and
danger
signals.
Proteolytic
cleavage
gasdermin
proteins
B-E
(GSDMB-GSDME)
well
established
as
trigger
pyroptosis,
but
the
intracellular
activation
mechanism
GSDMA
remains
elusive.
Here,
we
demonstrate
that
severe
starvation
induces
pyroptosis
through
phosphorylation-induced
GSDMA.
Nutrient
stresses
stimulate
via
phosphorylation
mediated
by
Unc-51-like
autophagy-activating
kinase
1
(ULK1).
Phosphorylation
Ser353
on
human
ULK1
or
phospho-mimetic
Ser353Asp
mutant
liberates
from
auto-inhibition,
facilitating
its
membrane
targeting
initiation
pyroptosis.
To
further
validate
significance
phosphorylation,
generated
constitutively
active
Ser354Asp
mouse
Gsdma,
which
induced
skin
inflammation
hyperplasia
in
mice,
reminiscent
phenotypes
with
activated
Gsdma.
This
study
uncovers
underlying
cellular
response
to
nutrient
stress.
Язык: Английский