International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(5), С. 1927 - 1946
Опубликована: Янв. 1, 2024
The
activation
of
NLRP3
inflammasome
in
microglia
is
critical
for
neuroinflammation
during
postoperative
cognitive
dysfunction
(POCD)
induced
by
sevoflurane.However,
the
molecular
mechanism
which
sevoflurane
activates
remains
unclear.The
cGAS-STING
pathway
an
evolutionarily
conserved
inflammatory
defense
mechanism.The
role
sevoflurane-induced
inflammasome-dependent
and
underlying
mechanisms
require
further
investigation.We
found
that
prolonged
anesthesia
with
triggered
characterized
vivo.Interestingly,
was
activated
hippocampus
mice
receiving
sevoflurane.While
blockade
cGAS
RU.521
attenuated
mice.In
vitro,
we
treatment
significantly
microglia,
while
pre-treatment
robustly
inhibited
activation.Mechanistically,
mitochondrial
fission
released
DNA
(mtDNA)
into
cytoplasm,
could
be
abolished
Mdivi-1.Blocking
mtDNA
release
via
mPTP-VDAC
channel
inhibitor
cytosolic
escape
reduced
finally
inhibiting
activation.Therefore,
regulating
targeting
may
provide
a
novel
therapeutic
target
POCD.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 10, 2024
The
emergence
of
single
nucleus
RNA
sequencing
(snRNA-seq)
offers
to
revolutionize
the
study
Alzheimer's
disease
(AD).
Integration
with
complementary
multiomics
data
such
as
genetics,
proteomics
and
clinical
provides
powerful
opportunities
link
cell
subpopulations
molecular
networks
a
broader
disease-relevant
context.
We
report
snRNA-seq
profiles
from
superior
frontal
gyrus
samples
101
well
characterized
subjects
Banner
Brain
Body
Donation
Program
in
combination
whole
genome
sequences.
findings
that
common
AD
risk
variants
CR1
expression
oligodendrocytes
alterations
hematological
parameters.
observed
an
AD-associated
CD83(+)
microglial
subtype
unique
which
is
associated
immunoglobulin
IgG4
production
transverse
colon.
Our
major
observations
were
replicated
two
additional,
independent
sets.
These
illustrate
power
multi-tissue
profiling
contextualize
brain
transcriptomics
reveal
biology.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 17, 2025
Multiple
sclerosis
(MS)
is
a
chronic
autoimmune,
inflammatory
and
neurodegenerative
disease
affecting
the
central
nervous
system
(CNS).
MS
associated
with
complex
interplay
between
processes,
mostly
attributed
to
pathogenic
T
B
cells.
However,
growing
body
of
preclinical
clinical
evidence
indicates
that
innate
immunity
plays
crucial
role
in
promotion
progression.
Accordingly,
studies
targeting
different
immune
cells
control
are
currently
under
study,
highlighting
importance
this
pathology.
Here,
we
reviewed
recent
findings
regarding
played
by
pathogenesis
MS.
Additionally,
discuss
potential
new
treatments
for
based
on
targets
against
components.
Life Science Alliance,
Год журнала:
2024,
Номер
7(10), С. e202402736 - e202402736
Опубликована: Июль 26, 2024
The
presence
of
HIV
in
sequestered
reservoirs
is
a
central
impediment
to
functional
cure,
allowing
persist
despite
life-long
antiretroviral
therapy
(ART),
and
driving
variety
comorbid
conditions.
Our
understanding
the
latent
reservoir
nervous
system
incomplete,
because
difficulties
accessing
human
tissues.
Microglia
contribute
reservoirs,
but
molecular
phenotype
HIV-infected
microglia
poorly
understood.
We
leveraged
unique
"Last
Gift"
rapid
autopsy
program,
which
people
with
are
closely
followed
until
days
or
even
hours
before
death.
Microglial
populations
were
heterogeneous
regarding
their
gene
expression
profiles
showed
similar
chromatin
accessibility
landscapes.
Despite
ART,
we
detected
occasional
containing
cell-associated
RNA
DNA
integrated
into
open
regions
host's
genome
(∼0.005%).
detectable
an
inflammatory
phenotype.
These
results
demonstrate
distinct
myeloid
cell
brains
suppressive
ART.
Strategies
for
curing
neurocognitive
impairment
will
need
consider
compartment
be
successful.
Cell Death and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 14, 2025
Abstract
Neuroinflammation
is
a
key
factor
in
the
pathogenesis
of
Parkinson’s
disease
(PD).
Activated
microglia
central
nervous
system
(CNS)
and
infiltration
peripheral
immune
cells
contribute
to
dopaminergic
neuron
loss.
However,
role
responses,
particularly
triggering
receptor
expressed
on
myeloid
cells-1
(TREM-1),
PD
remains
unclear.
Using
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
hydrochloride
(MPTP)-induced
mouse
model,
we
examined
TREM-1
expression
monocyte
substantia
nigra
pars
compacta
(SNpc).
We
found
that
MPTP
increased
monocytes,
deletion
monocytes
protected
against
neurotoxicity
SNpc.
inhibition,
both
genetically
pharmacologically,
reduced
infiltration,
alleviated
neuroinflammation,
preserved
neurons,
resulting
improved
motor
function.
Furthermore,
adoptive
transfer
TREM-1-expressing
from
model
mice
naive
induced
neuronal
damage
deficits.
These
results
underscore
critical
progression,
suggesting
targeting
could
be
promising
therapeutic
approach
prevent
neurodegeneration
dysfunction
PD.
