Acta Neuropathologica,
Год журнала:
2021,
Номер
143(2), С. 179 - 224
Опубликована: Дек. 1, 2021
Abstract
In
neurological
diseases,
the
actions
of
microglia,
resident
myeloid
cells
CNS
parenchyma,
may
diverge
from,
or
intersect
with,
those
recruited
monocytes
to
drive
immune-mediated
pathology.
However,
defining
precise
roles
each
cell
type
has
historically
been
impeded
by
lack
discriminating
markers
and
experimental
systems
capable
accurately
identifying
them.
Our
ability
distinguish
microglia
from
in
neuroinflammation
advanced
with
single-cell
technologies,
new
drugs
that
identify
deplete
them,
respectively.
Nevertheless,
focus
individual
studies
on
particular
types,
diseases
approaches
limited
our
connect
phenotype
function
more
widely
across
diverse
pathologies.
Here,
we
critically
review,
tabulate
integrate
disease-specific
functions
immune
profiles
provide
a
comprehensive
atlas
responses
viral
encephalitis,
demyelination,
neurodegeneration
ischemic
injury.
emphasizing
differential
severe
neuroinflammatory
disease
inflammatory
pathways
common
equally
incapacitating
less
inflammation.
We
examine
these
findings
context
human
highlight
benefits
inherent
limitations
animal
models
impede
facilitate
clinical
translation.
This
enables
us
contrasting,
non-redundant
often
opposing
could
be
targeted
therapeutically.
Cell Reports,
Год журнала:
2020,
Номер
30(5), С. 1271 - 1281
Опубликована: Фев. 1, 2020
Microglia
are
resident
immune
cells
in
the
central
nervous
system
(CNS)
that
capable
of
carrying
out
prominent
and
various
functions
during
development
adulthood
under
both
homeostatic
disease
conditions.
Although
microglia
traditionally
thought
to
be
heterogeneous
populations,
which
potentially
allows
them
achieve
a
wide
range
responses
environmental
changes
for
maintenance
CNS
homeostasis,
lack
unbiased
high-throughput
methods
assess
heterogeneity
has
prevented
study
spatially
temporally
distributed
subsets.
The
recent
emergence
novel
single-cell
techniques,
such
as
cytometry
by
time-of-flight
mass
spectrometry
(CyTOF)
RNA
sequencing,
enabled
scientists
overcome
limitations
reveal
surprising
context-dependent
microglia.
In
this
review,
we
summarize
current
knowledge
about
spatial,
temporal,
functional
diversity
development,
mice
humans.
Journal of Neuroinflammation,
Год журнала:
2021,
Номер
18(1)
Опубликована: Ноя. 6, 2021
Microglia
are
emerging
as
critical
regulators
of
neuronal
function
and
behavior
in
nearly
every
area
neuroscience.
Initial
reports
focused
on
classical
immune
functions
microglia
pathological
contexts,
however,
immunological
concepts
from
these
studies
have
been
applied
to
describe
neuro-immune
interactions
the
absence
disease,
injury,
or
infection.
Indeed,
terms
such
'microglia
activation'
'neuroinflammation'
used
ubiquitously
changes
disparate
contexts;
particularly
stress
research,
where
prompt
undue
comparisons
conditions.
This
creates
a
barrier
for
investigators
new
neuro-immunology
ultimately
hinders
our
understanding
effects
microglia.
As
more
seek
understand
role
neurobiology
behavior,
it
is
increasingly
important
develop
standard
methods
study
define
microglial
phenotype
function.
In
this
review,
we
summarize
primary
research
physiological
contexts.
Further,
propose
framework
better
microglia1
chronic
stress.
approach
will
enable
precise
characterization
different
which
should
facilitate
development
microglia-directed
therapeutics
psychiatric
neurological
disease.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Сен. 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.
Annual Review of Immunology,
Год журнала:
2021,
Номер
39(1), С. 251 - 277
Опубликована: Фев. 9, 2021
The
immune
system
of
the
central
nervous
(CNS)
consists
primarily
innate
cells.
These
are
highly
specialized
macrophages
found
either
in
parenchyma,
called
microglia,
or
at
CNS
interfaces,
such
as
leptomeningeal,
perivascular,
and
choroid
plexus
macrophages.
While
they
were
thought
phagocytes,
their
function
extends
well
beyond
simple
removal
cell
debris
during
development
diseases.
Brain-resident
cells
to
be
plastic,
long-lived,
host
an
outstanding
number
risk
genes
for
multiple
pathologies.
As
a
result,
now
considered
most
suitable
targets
modulating
Additionally,
recent
single-cell
technologies
enhanced
our
molecular
understanding
origins,
fates,
interactomes,
functional
statesduring
health
perturbation.
Here,
we
review
current
state
challenges
myeloid
biology
treatment
options
related
International Journal of Biological Sciences,
Год журнала:
2021,
Номер
17(9), С. 2181 - 2192
Опубликована: Янв. 1, 2021
Extracellular
neuritic
plaques
composed
of
amyloid‑β
(Aβ)
protein
and
intracellular
neurofibrillary
tangles
containing
phosphorylated
tau
are
the
two
hallmark
proteins
Alzheimer's
disease
(AD),
separate
neurotoxicity
these
in
AD
has
been
extensively
studied.
However,
interventions
that
target
Aβ
or
individually
have
not
yielded
substantial
breakthroughs.
The
interest
interactions
between
is
increasing,
but
related
drug
investigations
their
infancy.
This
review
discusses
how
accelerates
phosphorylation
possible
mechanisms
pathways
by
which
mediates
toxicity.
also
describes
synergistic
effects
on
microglial
cells
astrocytes.
Studies
suggest
coexistence
to
mechanism
facilitates
propagation
aggregation
plaques.
mediate
cognitive
dysfunction
patients
with
AD.
In
summary,
this
summarizes
recent
data
interplay
promote
a
better
understanding
roles
pathological
process
provide
new
insights
into
against
