Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Oct. 24, 2022
Abstract
Microglia
are
important
immune
cells
in
the
central
nervous
system
(CNS)
that
undergo
turnover
throughout
lifespan.
If
microglial
debris
is
not
removed
a
timely
manner,
accumulated
may
influence
CNS
function.
Clearance
of
crucial
for
homeostasis.
However,
underlying
mechanisms
remain
obscure.
We
here
investigate
how
dead
microglia
removed.
find
although
can
phagocytose
vitro,
territory-dependent
competition
hinders
microglia-to-microglial
engulfment
vivo.
In
contrast,
mainly
phagocytosed
by
astrocytes
brain,
facilitated
C4b
opsonization.
The
engulfed
fragments
then
degraded
via
RUBICON-dependent
LC3-associated
phagocytosis
(LAP),
form
noncanonical
autophagy.
Interference
with
C4b-mediated
and
subsequent
LAP
disrupt
removal
degradation
debris,
respectively.
Together,
we
elucidate
cellular
molecular
mice,
extending
knowledge
on
maintenance
Antioxidants,
Journal Year:
2020,
Volume and Issue:
9(8), P. 743 - 743
Published: Aug. 13, 2020
Neurodegenerative
disorders,
such
as
Alzheimer’s
disease,
are
a
global
public
health
burden
with
poorly
understood
aetiology.
Neuroinflammation
and
oxidative
stress
(OS)
undoubtedly
hallmarks
of
neurodegeneration,
contributing
to
disease
progression.
Protein
aggregation
neuronal
damage
result
in
the
activation
disease-associated
microglia
(DAM)
via
damage-associated
molecular
patterns
(DAMPs).
DAM
facilitate
persistent
inflammation
reactive
oxygen
species
(ROS)
generation.
However,
mechanisms
linking
OS
have
not
been
well-defined;
thus
targeting
these
cells
for
clinical
benefit
has
possible.
In
microglia,
ROS
generated
primarily
by
NADPH
oxidase
2
(NOX2)
NOX2
is
associated
DAMP
signalling,
amyloid
plaque
deposition,
especially
cerebrovasculature.
Additionally,
originating
from
both
NOX
mitochondria
may
act
second
messengers
propagate
immune
activation;
intracellular
signalling
underlie
excessive
OS.
Targeting
key
kinases
inflammatory
response
could
cease
promote
tissue
repair.
Expression
antioxidant
proteins
dehydrogenase
1
(NQO1),
promoted
transcription
factor
Nrf2,
which
functions
control
limit
Lipid
droplet
accumulating
(LDAM)
also
represent
double-edged
sword
neurodegenerative
sequestering
peroxidised
lipids
non-pathological
ageing
but
becoming
dysregulated
pro-inflammatory
disease.
We
suggest
that
future
studies
should
focus
on
targeted
manipulation
understand
driving
inflammatory-related
activation.
Finally,
we
discuss
recent
evidence
therapeutic
target
identification
be
unbiased
founded
relevant
pathophysiological
assays
discovery
translatable
anti-inflammatory
therapeutics.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Sept. 22, 2023
Abstract
Microglia
activation
is
observed
in
various
neurodegenerative
diseases.
Recent
advances
single-cell
technologies
have
revealed
that
these
reactive
microglia
were
with
high
spatial
and
temporal
heterogeneity.
Some
identified
specific
states
correlate
pathological
hallmarks
are
associated
functions.
both
exert
protective
function
by
phagocytosing
clearing
protein
aggregates
play
detrimental
roles
due
to
excessive
uptake
of
aggregates,
which
would
lead
microglial
phagocytic
ability
impairment,
neuroinflammation,
eventually
neurodegeneration.
In
addition,
peripheral
immune
cells
infiltration
shapes
into
a
pro-inflammatory
phenotype
accelerates
disease
progression.
also
act
as
mobile
vehicle
propagate
aggregates.
Extracellular
vesicles
released
from
autophagy
impairment
all
contribute
progression
Thus,
enhancing
phagocytosis,
reducing
microglial-mediated
inhibiting
exosome
synthesis
secretion,
promoting
conversion
considered
be
promising
strategies
for
the
therapy
Here
we
comprehensively
review
biology
diseases,
including
Alzheimer’s
disease,
Parkinson’s
multiple
system
atrophy,
amyotrophic
lateral
sclerosis,
frontotemporal
dementia,
progressive
supranuclear
palsy,
corticobasal
degeneration,
dementia
Lewy
bodies
Huntington’s
disease.
We
summarize
possible
microglia-targeted
interventions
treatments
against
diseases
preclinical
clinical
evidence
cell
experiments,
animal
studies,
trials.
Frontiers in Cellular Neuroscience,
Journal Year:
2021,
Volume and Issue:
15
Published: Sept. 13, 2021
Neuroinflammation
is
involved
in
the
onset
or
progression
of
various
neurodegenerative
diseases.
Initiation
neuroinflammation
triggered
by
endogenous
substances
(damage-associated
molecular
patterns)
and/or
exogenous
pathogens.
Activation
glial
cells
(microglia
and
astrocytes)
widely
recognized
as
a
hallmark
triggers
release
proinflammatory
cytokines,
leading
to
neurotoxicity
neuronal
dysfunction.
Another
feature
associated
with
neuroinflammatory
diseases
impairment
blood-brain
barrier
(BBB).
The
BBB,
which
composed
brain
endothelial
connected
tight
junctions,
maintains
homeostasis
protects
neurons.
Impairment
this
allows
trafficking
immune
plasma
proteins
into
parenchyma
subsequent
inflammatory
processes
brain.
Besides
neurons,
activated
also
affect
BBB
integrity.
Therefore,
dysfunction
can
amplify
act
key
process
development
neuroinflammation.
integrity
determined
integration
multiple
signaling
pathways
within
through
intercellular
communication
between
perivascular
(pericytes,
astrocytes,
microglia,
oligodendrocytes).
For
prevention
disruption,
both
cellular
components,
such
molecules
cells,
non-cellular
mediators
released
should
be
considered.
Thus,
understanding
intracellular
that
disrupt
provide
novel
treatments
for
neurological
In
review,
we
discuss
current
knowledge
regarding
underlying
mechanisms
cells.
Circulation Research,
Journal Year:
2022,
Volume and Issue:
130(8), P. 1204 - 1229
Published: April 14, 2022
Intracerebral
hemorrhage
(ICH)
is
a
devastating
form
of
stroke
with
high
morbidity
and
mortality.
This
review
article
focuses
on
the
epidemiology,
cause,
mechanisms
injury,
current
treatment
strategies,
future
research
directions
ICH.
Incidence
hemorrhagic
has
increased
worldwide
over
past
40
years,
shifts
in
cause
time
as
hypertension
management
improved
anticoagulant
use
increased.
Preclinical
clinical
trials
have
elucidated
underlying
ICH
injury
from
including
complex
interaction
between
edema,
inflammation,
iron-induced
oxidative
stress.
Several
investigated
optimal
medical
surgical
without
clear
improvement
survival
functional
outcomes.
Ongoing
into
novel
approaches
for
provide
hope
reducing
effect
this
disease
future.
Areas
promise
therapy
include
prognostic
biomarkers
primary
prevention
based
pathobiology,
ultra-early
hemostatic
therapy,
minimally
invasive
surgery,
perihematomal
protection
against
inflammatory
brain
injury.
Journal of the American College of Cardiology,
Journal Year:
2020,
Volume and Issue:
75(8), P. 942 - 951
Published: Feb. 24, 2020
Alzheimer's
disease,
the
leading
cause
of
dementia
in
elderly,
is
a
neurodegenerative
condition
characterized
by
accumulation
amyloid
plaques
and
neurofibrillary
tangles
brain.
However,
age-related
vascular
changes
accompany
or
even
precede
development
pathology,
raising
possibility
that
they
may
have
pathogenic
role.
This
review
provides
an
appraisal
alterations
cerebral
systemic
vasculature,
heart,
hemostasis
occur
disease
their
relationships
to
cognitive
impairment.
Although
molecular
pathogenesis
these
remains
be
defined,
amyloid-β
likely
contributor
brain
as
heart.
Collectively,
evidence
suggests
pathology
dementia,
including
inextricably
linked
onset
progression.
Consequently,
contribution
factors
should
considered
preventive,
diagnostic,
therapeutic
approaches
address
one
major
health
challenges
our
time.
Alzheimer s & Dementia,
Journal Year:
2019,
Volume and Issue:
16(4), P. 681 - 695
Published: Dec. 24, 2019
We
investigated
plasma
proteomic
markers
of
astrocytopathy,
brain
degeneration,
plasticity,
and
inflammation
in
sporadic
early-onset
versus
late-onset
Alzheimer's
disease
(EOAD
LOAD).