Frontiers in Immunology,
Journal Year:
2019,
Volume and Issue:
10
Published: Oct. 25, 2019
Inflammasomes
play
a
crucial
role
in
innate
immunity
by
serving
as
signaling
platforms
which
deal
with
plethora
of
pathogenic
products
and
cellular
associated
stress
damage.
By
far,
the
best
studied
most
characterized
inflammasome
is
NLRP3
inflammasome,
consists
(nucleotide-binding
domain
leucine-rich
repeat
(NLR)
pyrin
containing
receptor
3),
ASC
(apoptosis-associated
speck-like
protein
caspase
recruitment
domain),
procaspase-1.
Activation
mediated
highly
diverse
stimuli.
Upon
activation,
recruits
adapter
protein,
procaspase-1
resulting
its
cleavage
inducing
maturation,
secretion
inflammatory
cytokines
pyroptosis.
However,
aberrant
activation
implicated
various
diseases
including
diabetes,
atherosclerosis,
metabolic
syndrome,
cardiovascular,
neurodegenerative
diseases;
raising
tremendous
clinical
interest
exploring
potential
inhibitors
inflammasome.
Recent
investigations
have
disclosed
pathway
were
validated
through
Oxidative Medicine and Cellular Longevity,
Journal Year:
2020,
Volume and Issue:
2020, P. 1 - 11
Published: Feb. 18, 2020
Almost
all
human
diseases
are
strongly
associated
with
inflammation,
and
a
deep
understanding
of
the
exact
mechanism
is
helpful
for
treatment.
The
NLRP3
inflammasome
composed
protein,
procaspase-1,
ASC
plays
vital
role
in
regulating
inflammation.
In
this
review,
regulation
activation,
its
proinflammatory
inflammatory
diseases,
interactions
autophagy,
targeted
therapeutic
approaches
will
be
summarized.
Frontiers in Aging Neuroscience,
Journal Year:
2022,
Volume and Issue:
14
Published: June 10, 2022
The
NLRP3
inflammasome
is
a
multiprotein
complex
that
plays
pivotal
role
in
regulating
the
innate
immune
system
and
inflammatory
signaling.
Upon
activation
by
PAMPs
DAMPs,
oligomerizes
activates
caspase-1
which
initiates
processing
release
of
pro-inflammatory
cytokines
IL-1β
IL-18.
most
extensively
studied
to
date
due
its
array
activators
aberrant
several
diseases.
Studies
using
small
molecules
biologics
targeting
pathway
have
shown
positive
outcomes
treating
various
disease
pathologies
blocking
chronic
inflammation.
In
this
review,
we
discuss
recent
advances
understanding
mechanism,
pathology,
provide
broad
review
therapeutics
discovered
target
their
challenges.
Journal of Neuroscience,
Journal Year:
2020,
Volume and Issue:
40(14), P. 2960 - 2974
Published: Feb. 24, 2020
Chronic
neuroinflammation
with
sustained
microglial
activation
occurs
following
severe
traumatic
brain
injury
(TBI)
and
is
believed
to
contribute
subsequent
neurodegeneration
neurological
deficits.
Microglia,
the
primary
innate
immune
cells
in
brain,
are
dependent
on
colony
stimulating
factor
1
receptor
(CSF1R)
signaling
for
their
survival.
In
this
preclinical
study,
we
examined
effects
of
delayed
depletion
chronically
activated
microglia
functional
recovery
up
3
months
postinjury.
A
CSF1R
inhibitor,
Plexxikon
(PLX)
5622,
was
administered
adult
male
C57BL/6J
mice
at
month
after
controlled
cortical
impact
remove
microglia,
inhibitor
withdrawn
1-week
later
allow
repopulation.
Following
TBI,
repopulated
displayed
a
ramified
morphology
similar
that
Sham
uninjured
mice,
whereas
vehicle-treated
TBI
showed
typical
chronic
posttraumatic
hypertrophic
morphology.
PLX5622
treatment
limited
TBI-associated
neuropathological
changes
postinjury;
these
included
smaller
lesion,
reduced
hippocampal
neuron
cell
death,
decreased
NOX2-
NLRP3
inflammasome-associated
neuroinflammation.
Furthermore,
led
widespread
transcriptome
altered
gene
pathways
involved
neuroinflammation,
oxidative
stress,
neuroplasticity.
Using
variety
complementary
neurobehavioral
tests,
PLX5622-treated
also
had
improved
long-term
motor
cognitive
function
through
Together,
studies
demonstrate
phase
removal
neurotoxic
using
inhibitors
markedly
reduce
associated
neurodegeneration,
as
well
related
SIGNIFICANCE
STATEMENT
Traumatic
debilitating
disorder
can
seriously
patient's
quality
life.
Microglial-mediated
induced
contributes
deficits
on-going
neurodegenerative
processes.
Here,
investigated
effect
breaking
neuroinflammatory
loop
1-month
by
pharmacological
5622.
Overall,
show
short-term
elimination
during
followed
repopulation
results
improvements
function,
suppression
stress
pathways,
reduction
persistent
These
clinically
relevant
support
new
concepts
therapeutic
window
may
be
far
longer
than
traditionally
if
evolving
microglial-mediated
inhibited
or
regulated
precise
manner.
Journal of Neuroinflammation,
Journal Year:
2020,
Volume and Issue:
17(1)
Published: April 6, 2020
There
is
a
great
clinical
need
to
identify
the
underlying
mechanisms,
as
well
related
biomarkers,
and
treatment
targets,
for
traumatic
brain
injury
(TBI).
Neuroinflammation
central
pathophysiological
feature
of
TBI.
NLRP3
inflammasome
activity
necessary
component
innate
immune
response
tissue
damage,
dysregulated
has
been
implicated
in
number
neurological
conditions.
This
paper
introduces
its
implication
pathogenesis
neuroinflammatory-related
conditions,
with
particular
focus
on
Although
role
TBI
only
recently
identified,
findings
suggest
that
priming
activation
are
upregulated
following
Moreover,
recent
studies
utilizing
specific
inhibitors
have
provided
further
evidence
this
major
driver
neuroinflammation
neurobehavioral
disturbances
In
addition,
there
emerging
circulating
inflammasome-associated
proteins
may
utility
diagnostic
biomarkers
neuroinflammatory
including
Finally,
novel
promising
areas
research
will
be
highlighted,
potential
involvement
mild
TBI,
how
factors
such
biological
sex
affect
use
biomarker
platforms.
Taken
together,
review
highlights
exciting
target
treatments
ultimately
used
improve
management.
Frontiers in Aging Neuroscience,
Journal Year:
2022,
Volume and Issue:
14
Published: March 25, 2022
Traumatic
brain
injury
(TBI)
is
one
of
the
most
common
diseases
in
central
nervous
system
(CNS)
with
high
mortality
and
morbidity.
Patients
TBI
usually
suffer
many
sequelae
life
time
post
injury,
including
neurodegenerative
disorders
such
as
Alzheimer’s
disease
(AD)
Parkinson’s
(PD).
However,
pathological
mechanisms
connecting
these
two
processes
have
not
yet
been
fully
elucidated.
It
important
to
further
investigate
pathophysiological
underlying
TBI-induced
neurodegeneration,
which
will
promote
development
precise
treatment
target
for
notorious
consequences
after
TBI.
A
growing
body
evidence
shows
that
neuroinflammation
a
pivotal
process
chronic
neurodegeneration
following
Microglia,
immune
cells
CNS,
play
crucial
roles
other
CNS
diseases.
Of
interest,
microglial
activation
functional
alteration
has
proposed
key
mediators
evolution
pathology
Here,
we
review
updated
studies
involving
phenotypical
alterations
microglia
survey
molecules
regulating
activities
responses
pathology,
explore
their
potential
implications
injury.
The
work
give
us
comprehensive
understanding
driving
TBI-related
offer
novel
ideas
developing
corresponding
prevention
strategies
this
disease.
Frontiers in Pharmacology,
Journal Year:
2022,
Volume and Issue:
13
Published: Feb. 16, 2022
Alzheimer's
disease
(AD)
is
a
common
age-related
neurodegenerative
characterized
by
progressive
cognitive
dysfunction
and
behavioral
impairment.
The
typical
pathological
characteristics
of
AD
are
extracellular
senile
plaques
composed
amyloid
ß
(Aβ)
protein,
intracellular
neurofibrillary
tangles
formed
the
hyperphosphorylation
microtubule-associated
protein
tau,
neuron
loss.
In
past
hundred
years,
although
human
beings
have
invested
lot
manpower,
material
financial
resources,
there
no
widely
recognized
drug
for
effective
prevention
clinical
cure
in
world
so
far.
Therefore,
evaluating
exploring
new
targets
treatment
an
important
topic.
At
present,
researchers
not
stopped
pathogenesis
AD,
views
on
pathogenic
factors
constantly
changing.
Multiple
evidence
confirmed
that
chronic
neuroinflammation
plays
crucial
role
AD.
field
neuroinflammation,
nucleotide-binding
oligomerization
domain-like
receptor
pyrin
domain-containing
3
(NLRP3)
inflammasome
key
molecular
link
neuroinflammatory
pathway.
Under
stimulation
Aβ
oligomers
tau
aggregates,
it
can
lead
to
assembly
activation
NLRP3
microglia
astrocytes
brain,
thereby
causing
caspase-1
secretion
IL-1β
IL-18,
which
ultimately
triggers
pathophysiological
changes
decline
this
review,
we
summarize
current
literatures
activation-related
regulation
mechanisms,
discuss
its
possible
roles
Moreover,
focusing
combining
with
upstream
downstream
signaling
pathway-related
molecules
as
targets,
review
pharmacologically
related
various
methods
alleviate
regulating
inflammasome,
provides
ideas
Frontiers in Molecular Neuroscience,
Journal Year:
2022,
Volume and Issue:
15
Published: Oct. 24, 2022
Neurological
degeneration
after
neuroinflammation,
such
as
that
resulting
from
Alzheimer’s
disease
(AD),
stroke,
multiple
sclerosis
(MS),
and
post-traumatic
brain
injury
(TBI),
is
typically
associated
with
high
mortality
morbidity
permanent
cognitive
dysfunction,
which
places
a
heavy
economic
burden
on
families
society.
Diagnosing
curing
these
diseases
in
their
early
stages
remains
challenge
for
clinical
investigation
treatment.
Recent
insight
into
the
onset
progression
of
highlights
permeability
blood–brain
barrier
(BBB).
The
primary
factor
influences
BBB
structure
function
inflammation,
especially
main
cytokines
including
IL-1β,
TNFα,
IL-6,
mechanism
disruption
are
critical
component
aforementioned
diseases.
Surprisingly,
systematic
inflammation
can
also
induce
much
worse
neurological
or
injuries
do.
In
this
review,
we
will
therefore
discuss
physiological
BBB,
recent
research
about
inducing
impairment,
eventually
need
to
prevent
BBB.
Pharmacological Reviews,
Journal Year:
2023,
Volume and Issue:
75(3), P. 487 - 520
Published: Jan. 20, 2023
The
nucleotide-binding,
oligomerization
domain-like
receptor
family
pyrin
domain
containing
3
(NLRP3)
inflammasome
is
a
multi-protein
complex
that
combines
sensing,
regulation,
and
effector
functions
to
regulate
inflammation
in
health
disease.
NLRP3
activated
by
diverse
range
of
inflammation-instigating
signals
known
as
pathogen
associated
molecular
patterns
danger
patterns.
Upon
activation,
oligomerizes
recruits
partner
proteins
form
supramolecular
platform
process
the
maturation
release
interleukin
(IL)-1β,
IL-18,
gasdermin
D,
major
mediators
inflammatory
cell
death
termed
pyroptosis.
has
been
implicated
pathogenesis
wide
disease
conditions,
including
chronic
are
with
lifestyle
dietary
changes,
aging,
environmental
exposures
have
become
leading
cause
worldwide.
Pharmacological
targeting
signaling
demonstrated
promising
efficacy
ameliorating
list
conditions
animal
models.
These
findings
underscore
potential
importance
druggable
target
for
treating
diseases.
In
this
review,
recent
progress
understanding
structure
mechanism
action
discussed
focus
on
pharmacological
inhibition
small
molecule
inhibitors.
New
structural
mechanistic
insights
into
activation
inhibitor-NLRP3
interactions
would
aid
rational
design
evaluation
inhibitors
treatment
human
Significance
Statement
plays
central
role
innate
immune
sensing
control
inflammation.
diseases
Recent
elucidation
inhibitor
binding
generated
new
its
mode
interaction
at
levels,
providing
framework
developing
chemical
improved
specificity
against
concerns
