Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 12, 2024
NOD-like
receptor
protein
3
(NLRP3)
inflammasome
is
an
intracellular
sensing
complex
that
possesses
NACHT,
leucine-rich
repeat,
and
pyrin
domain,
playing
a
crucial
role
in
innate
immunity.
Activation
of
the
NLRP3
leads
to
production
pro-inflammatory
cellular
contents,
such
as
interleukin
(IL)-1β
IL-18,
induction
inflammatory
cell
death
known
pyroptosis,
thereby
amplifying
or
sustaining
inflammation.
While
balanced
response
beneficial
for
resolving
damage
promoting
tissue
healing,
excessive
activation
pyroptosis
can
have
harmful
effects.
The
involvement
has
been
observed
various
cardiovascular
diseases
(CVD).
Indeed,
its
associated
are
closely
linked
key
risk
factors
including
hyperlipidemia,
diabetes,
hypertension,
obesity,
hyperhomocysteinemia.
Exercise
compared
with
medicine
highly
effective
measure
both
preventing
treating
CVD.
Interestingly,
emerging
evidence
suggests
exercise
improves
CVD
inhibits
activity
pyroptosis.
In
this
review,
mechanisms
pathogenic
critically
discussed.
Importantly,
purpose
emphasize
managing
by
suppressing
proposes
it
foundation
developing
novel
treatment
strategies.
Nano-Micro Letters,
Год журнала:
2024,
Номер
16(1)
Опубликована: Фев. 19, 2024
Dry
eye
disease
(DED)
is
a
major
ocular
pathology
worldwide,
causing
serious
discomfort
and
even
visual
impairment.
The
incidence
of
DED
gradually
increasing
with
the
high-frequency
use
electronic
products.
Although
inflammation
core
cause
vicious
cycle,
reactive
oxygen
species
(ROS)
play
pivotal
role
in
cycle
by
regulating
from
upstream.
Therefore,
current
therapies
merely
targeting
show
failure
treatment.
Here,
novel
dual-atom
nanozymes
(DAN)-based
drops
are
developed.
antioxidative
DAN
successfully
prepared
embedding
Fe
Mn
bimetallic
single-atoms
N-doped
carbon
material
modifying
it
hydrophilic
polymer.
vitro
vivo
results
demonstrate
endowed
superior
biological
activity
scavenging
excessive
ROS,
inhibiting
NLRP3
inflammasome
activation,
decreasing
proinflammatory
cytokines
expression,
suppressing
cell
apoptosis.
Consequently,
effectively
alleviate
inflammation,
promote
corneal
epithelial
repair,
recover
goblet
density
tear
secretion,
thus
breaking
cycle.
Our
findings
open
an
avenue
to
make
as
intervention
form
ROS-mediated
inflammatory
diseases.
Neuropharmacology,
Год журнала:
2024,
Номер
252, С. 109941 - 109941
Опубликована: Март 31, 2024
Every
year,
10
million
people
develop
dementia,
the
most
common
of
which
is
Alzheimer's
disease
(AD).
To
date,
there
no
way
to
prevent
cognitive
decline
and
therapies
are
limited.
This
review
provides
a
neuroimmunological
perspective
on
progression
AD,
discusses
immune-targeted
that
in
preclinical
clinical
trials
may
impact
development
this
disease.
Specifically,
we
look
role
NLRP3
inflammasome,
its
triggers
brain
how
activation
can
contribute
dementia.
We
summarise
range
inhibitors
targeting
inflammasome
downstream
pathways
under
investigation,
discuss
future
therapeutic
perspectives
for
devastating
condition.
npj Metabolic Health and Disease,
Год журнала:
2024,
Номер
2(1)
Опубликована: Май 27, 2024
Abstract
The
ability
of
mitochondria
to
transform
the
energy
we
obtain
from
food
into
cell
phosphorylation
potential
has
long
been
appreciated.
However,
recent
decades
have
seen
an
evolution
in
our
understanding
mitochondria,
highlighting
their
significance
as
key
signal-transducing
organelles
with
essential
roles
immunity
that
extend
beyond
bioenergetic
function.
Importantly,
retain
bacterial
motifs
a
remnant
endosymbiotic
origin
are
recognised
by
innate
immune
cells
trigger
inflammation
and
participate
anti-microbial
defence.
This
review
aims
explore
how
mitochondrial
physiology,
spanning
oxidative
(OxPhos)
signalling
nucleic
acids,
metabolites,
lipids,
influences
effector
functions
phagocytes.
These
myriad
include
macrophage
polarisation,
efferocytosis,
anti-bactericidal
activity,
antigen
presentation,
signalling,
cytokine
regulation.
Strict
regulation
these
processes
is
critical
for
organismal
homeostasis
when
disrupted
may
cause
injury
or
contribute
disease.
Thus,
expanding
body
literature,
which
continues
highlight
central
role
system,
provide
insights
development
next
generation
therapies
inflammatory
diseases.
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Март 4, 2025
The
relationship
between
Alzheimer's
disease
(AD)
and
neuroimmunity
has
gradually
begun
to
be
unveiled.
Emerging
evidence
indicates
that
cyclic
GMP-AMP
synthase
(cGAS)
acts
as
a
cytosolic
DNA
sensor,
recognizing
damage-associated
molecular
patterns
(DAMPs),
inducing
the
innate
immune
response
by
activating
stimulator
of
interferon
genes
(STING).
Dysregulation
this
pathway
culminates
in
AD-related
neuroinflammation
neurodegeneration.
A
substantial
body
mitochondria
are
involved
critical
pathogenic
mechanisms
AD,
whose
damage
leads
release
mitochondrial
(mtDNA)
into
extramitochondrial
space.
This
leaked
mtDNA
serves
DAMP,
various
pattern
recognition
receptors
defense
networks
brain,
including
cGAS-STING
pathway,
ultimately
leading
an
imbalance
homeostasis.
Therefore,
modulation
mtDNA-cGAS-STING
restore
neuroimmune
homeostasis
may
offer
promising
prospects
for
improving
AD
treatment
outcomes.
In
review,
we
focus
on
during
stress
activation
pathway.
Additionally,
delve
research
progress
further
discuss
primary
directions
potential
hurdles
developing
targeted
therapeutic
drugs,
gain
deeper
understanding
pathogenesis
provide
new
approaches
its
therapy.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 29, 2025
Ferroptosis
is
a
form
of
iron-dependent
programmed
cell
death,
which
distinct
from
apoptosis,
necrosis,
and
autophagy.
Mitochondria
play
critical
role
in
initiating
amplifying
ferroptosis
cancer
cells.
Voltage-Dependent
Anion
Channel
1
(VDAC1)
embedded
the
mitochondrial
outer
membrane,
exerts
roles
regulation
ferroptosis.
However,
mechanisms
VDAC1
oligomerization
regulating
are
not
well
elucidated.
Here,
we
identify
that
binding
protein
V-Set
Transmembrane
Domain
Containing
2
Like
(VSTM2L),
mainly
localized
to
mitochondria,
positively
associated
with
prostate
(PCa)
progression,
key
regulator
Moreover,
VSTM2L
knockdown
PCa
cells
enhances
sensitivity
RSL3-induced
Mechanistically,
forms
complex
hexokinase
(HK2),
enhancing
their
affinity
preventing
oligomerization,
thereby
inhibiting
maintaining
mitochondria
homeostasis
vitro
vivo.
Collectively,
our
findings
reveal
pivotal
for
mitochondria-localized
driving
resistance
highlight
its
potential
as
ferroptosis-inducing
therapeutic
target
treatment
PCa.
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Фев. 7, 2025
Mitochondrial
dysfunction
is
a
pivotal
instigator
of
neuroinflammation,
with
mitochondrial
DNA
(mtDNA)
leakage
as
critical
intermediary.
This
review
delineates
the
intricate
pathways
leading
to
mtDNA
release,
which
include
membrane
permeabilization,
vesicular
trafficking,
disruption
homeostatic
regulation,
and
abnormalities
in
dynamics.
The
escaped
activates
cytosolic
sensors,
especially
cyclic
gmp-amp
synthase
(cGAS)
signalling
inflammasome,
initiating
neuroinflammatory
cascades
via
pathways,
exacerbating
spectrum
neurological
pathologies.
therapeutic
promise
targeting
discussed
detail,
underscoring
necessity
for
multifaceted
strategy
that
encompasses
preservation
homeostasis,
prevention
leakage,
reestablishment
dynamics,
inhibition
activation
sensors.
Advancing
our
understanding
complex
interplay
between
neuroinflammation
imperative
developing
precision
interventions
disorders.
Nature Metabolism,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 19, 2025
Abstract
Macrophages
stimulated
by
lipopolysaccharide
(LPS)
generate
mitochondria-derived
reactive
oxygen
species
(mtROS)
that
act
as
antimicrobial
agents
and
redox
signals;
however,
the
mechanism
of
LPS-induced
mitochondrial
superoxide
generation
is
unknown.
Here
we
show
LPS-stimulated
bone-marrow-derived
macrophages
produce
reverse
electron
transport
(RET)
at
complex
I
chain.
Using
chemical
biology
genetic
approaches,
demonstrate
production
driven
metabolic
reprogramming,
which
increases
proton
motive
force
(∆p),
primarily
elevated
membrane
potential
(Δψ
m
)
maintains
a
reduced
CoQ
pool.
The
key
changes
are
repurposing
ATP
from
oxidative
phosphorylation
to
glycolysis,
reduces
reliance
on
F
1
O
-ATP
synthase
activity
resulting
in
higher
∆p,
while
oxidation
succinate
sustains
Furthermore,
mtROS
RET
regulates
IL-1β
release
during
NLRP3
inflammasome
activation.
Thus,
ROS
generated
an
important
signal
macrophage
cytokine
production.
ACS Nano,
Год журнала:
2023,
Номер
17(22), С. 22960 - 22978
Опубликована: Ноя. 6, 2023
Infected
bone
defects
(IBDs)
exhibit
impaired
healing
due
to
excessive
inflammation
triggered
by
pathogen-associated
molecular
patterns
(PAMPs)
from
bacteria.
As
a
vital
factor
in
orchestrating
immune
responses,
mitochondrial
homeostasis
maintenance
is
central
blockade.
This
research
developed
chameleon-like
nanoplatform
covering
hydroxyapatite
nanoparticles
with
cerium
ion
coordinated
tannic
acid
supramolecular
network
(HA@Ce-TA),
which
adaptively
functions
regulate
based
on
intra-
and
extracellular
environments.
Extracellularly,
acidic
conditions
activate
HA@Ce-TA's
peroxidase/oxidase-mimicking
activity
produce
reactive
oxygen
species
(ROS),
external
near-infrared
(NIR)
irradiation
excites
nanoscale
Ce-TA
hyperthermia,
found
explained
chemical
computation.
ROS
production
photothermal
therapy
can
eliminate
bacteria
effectively
reduce
stress.
Intracellularly,
HA@Ce-TA
remodels
dynamics
upregulating
fusion
genes
eliminates
mimicking
superoxidase/catalase.
Consequently,
this
comprehensive
modulation
of
inhibits
inflammasome
overactivation.
In
vitro
vivo
studies
showed
modulate
the
mitochondria-centered
inflammatory
cascade
enhance
IBD
treatment,
highlighting
potential
engineering
nanotherapeutics
recalibrate
as
an
infected
disease-modifying
intervention.