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.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Июль 19, 2022
Recently,
a
large
number
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
variants
continuously
emerged
and
posed
major
threat
to
global
public
health.
Among
them,
particularly,
Omicron
variant
(B.1.1.529),
first
identified
in
November
2021,
carried
numerous
mutations
its
spike
protein
(S),
then
quickly
spread
around
the
world.
Currently,
has
expanded
into
more
than
one
hundred
sublineages,
such
as
BA.1,
BA.2,
BA.2.12.1,
BA.4
BA.5,
which
have
already
become
globally
dominant
variants.
Different
from
other
concern
(VOCs)
SARS-CoV-2,
sublineages
exhibit
increased
transmissibility
immune
escape
neutralizing
antibodies
generated
through
previous
infection
or
vaccination,
caused
re-infections
breakthrough
infections.
In
this
prospective,
we
focused
on
origin,
virological
features,
evasion
intervention
will
benefit
development
next-generation
vaccines
therapeutics,
including
pan-sarbecovirus
universal
anti-CoV
combat
currently
circulating
future
emerging
well
SARS-CoV-2
Cellular & Molecular Biology Letters,
Год журнала:
2023,
Номер
28(1)
Опубликована: Июнь 27, 2023
The
NOD-like
receptor
protein
3
(NLRP3)
inflammasome
is
a
complex
that
regulates
innate
immune
responses
by
activating
caspase-1
and
the
inflammatory
cytokines
interleukin
(IL)-1β
IL-18.
Multiple
studies
have
demonstrated
importance
of
NLRP3
in
development
inflammation-related
diseases,
including
arthritis,
Alzheimer's
disease,
bowel
other
autoimmune
autoinflammatory
diseases.
This
review
first
explains
activation
regulatory
mechanism
inflammasome.
Secondly,
we
focus
on
role
various
Finally,
look
forward
to
new
methods
for
targeting
treat
provide
ideas
clinical
treatment.
Molecular Psychiatry,
Год журнала:
2022,
Номер
28(7), С. 2878 - 2893
Опубликована: Ноя. 1, 2022
Coronavirus
disease-2019
(COVID-19)
is
primarily
a
respiratory
disease,
however,
an
increasing
number
of
reports
indicate
that
SARS-CoV-2
infection
can
also
cause
severe
neurological
manifestations,
including
precipitating
cases
probable
Parkinson's
disease.
As
microglial
NLRP3
inflammasome
activation
major
driver
neurodegeneration,
here
we
interrogated
whether
promote
activation.
Using
transgenic
mice
expressing
human
angiotensin-converting
enzyme
2
(hACE2)
as
COVID-19
pre-clinical
model,
established
the
presence
virus
in
brain
together
with
and
upregulation
comparison
to
uninfected
mice.
Next,
utilising
model
monocyte-derived
microglia,
identified
isolates
bind
enter
microglia
absence
viral
replication.
This
interaction
directly
induced
robust
activation,
even
another
priming
signal.
Mechanistically,
demonstrated
purified
spike
glycoprotein
activated
LPS-primed
ACE2-dependent
manner.
Spike
protein
could
prime
through
NF-κB
signalling,
allowing
for
either
ATP,
nigericin
or
α-synuclein.
Notably,
protein-mediated
was
significantly
enhanced
α-synuclein
fibrils
entirely
ablated
by
NLRP3-inhibition.
Finally,
demonstrate
infected
hACE2
treated
orally
post-infection
inhibitory
drug
MCC950,
have
reduced
increased
survival
untreated
These
results
support
possible
mechanism
innate
immune
SARS-CoV-2,
which
explain
vulnerability
developing
symptoms
akin
disease
individuals,
potential
therapeutic
avenue
intervention.
Cell Death and Differentiation,
Год журнала:
2022,
Номер
29(6), С. 1107 - 1122
Опубликована: Май 17, 2022
Abstract
The
coronavirus
disease
2019
(COVID-19)
has
been
a
global
pandemic
for
more
than
2
years
and
it
still
impacts
our
daily
lifestyle
quality
in
unprecedented
ways.
A
better
understanding
of
immunity
its
regulation
response
to
SARS-CoV-2
infection
is
urgently
needed.
Based
on
the
current
literature,
we
review
here
various
virus
mutations
evolving
manifestations
along
with
alterations
immune
responses
specific
focuses
innate
response,
neutrophil
extracellular
traps,
humoral
immunity,
cellular
immunity.
Different
types
vaccines
were
compared
analyzed
based
their
unique
properties
elicit
Various
therapeutic
strategies
such
as
antibody,
anti-viral
medications
inflammation
control
discussed.
We
predict
that
available
continuously
emerging
new
technologies,
powerful
administration
schedules,
effective
public
health
measures,
COVID-19
will
be
under
near
future.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(15)
Опубликована: Июль 31, 2022
SARS-CoV-2–infected
individuals
may
suffer
a
multi–organ
system
disorder
known
as
"long
COVID"
or
post-acute
sequelae
of
SARS-CoV-2
infection
(PASC).
There
are
no
standard
treatments,
the
pathophysiology
is
unknown,
and
incidence
varies
by
clinical
phenotype.
Acute
COVID-19
correlates
with
biomarkers
systemic
inflammation,
hypercoagulability,
comorbidities
that
less
prominent
in
PASC.
Macrovessel
thrombosis,
hallmark
acute
COVID-19,
frequent
Female
sex
at
birth
associated
reduced
risk
for
progression,
but
increased
Persistent
microvascular
endotheliopathy
cryptic
tissue
reservoirs
has
been
implicated
PASC
pathology.
Autoantibodies,
localized
reactivation
latent
pathogens
also
be
involved,
potentially
leading
to
documented
multiple
tissues.
Diagnostic
assays
illuminating
possible
therapeutic
targets
discussed.
