Molecular Neurodegeneration,
Год журнала:
2022,
Номер
17(1)
Опубликована: Дек. 23, 2022
Abstract
Microglia
are
central
players
in
brain
innate
immunity
and
have
been
the
subject
of
extensive
research
Alzheimer’s
disease
(AD).
In
this
review,
we
aim
to
summarize
genetic
functional
discoveries
that
advanced
our
understanding
microglia
reactivity
AD
pathology.
Given
heightened
risk
posed
by
rare
variants
microglial
triggering
receptor
expressed
on
myeloid
cells
2
(TREM2),
will
focus
studies
addressing
impact
responses
amyloid
plaques,
tauopathy
demyelination
pathologies
mouse
human.
Finally,
discuss
implications
recent
TREM2
biology
potential
therapeutic
strategies
for
AD.
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.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 16, 2024
Abstract
The
human
gastrointestinal
tract
is
populated
with
a
diverse
microbial
community.
vast
genetic
and
metabolic
potential
of
the
gut
microbiome
underpins
its
ubiquity
in
nearly
every
aspect
biology,
including
health
maintenance,
development,
aging,
disease.
advent
new
sequencing
technologies
culture-independent
methods
has
allowed
researchers
to
move
beyond
correlative
studies
toward
mechanistic
explorations
shed
light
on
microbiome–host
interactions.
Evidence
unveiled
bidirectional
communication
between
central
nervous
system,
referred
as
“microbiota–gut–brain
axis”.
microbiota–gut–brain
axis
represents
an
important
regulator
glial
functions,
making
it
actionable
target
ameliorate
development
progression
neurodegenerative
diseases.
In
this
review,
we
discuss
mechanisms
As
provides
essential
cues
microglia,
astrocytes,
oligodendrocytes,
examine
communications
microbiota
these
cells
during
healthy
states
Subsequently,
diseases
using
metabolite-centric
approach,
while
also
examining
role
microbiota-related
neurotransmitters
hormones.
Next,
targeting
intestinal
barrier,
blood–brain
meninges,
peripheral
immune
system
counteract
dysfunction
neurodegeneration.
Finally,
conclude
by
assessing
pre-clinical
clinical
evidence
probiotics,
prebiotics,
fecal
transplantation
A
thorough
comprehension
will
foster
effective
therapeutic
interventions
for
management
Ageing Research Reviews,
Год журнала:
2021,
Номер
72, С. 101464 - 101464
Опубликована: Сен. 20, 2021
Alzheimer's
disease
(AD)
is
a
complex
neurodegenerative
in
the
elderly
and
most
common
cause
of
human
dementia.
AD
characterized
by
accumulation
abnormal
protein
aggregates
including
amyloid
plaques
(composed
beta-amyloid
(Aβ)
peptides)
neurofibrillary
tangles
(formed
hyper-phosphorylated
tau
protein).
Synaptic
plasticity,
neuroinflammation,
calcium
signaling
etc.
also
show
dysfunction
patients.
Autophagy
an
evolutionarily
conserved
lysosome-dependent
cellular
event
eukaryotes.
It
closely
linked
to
modulation
metabolism,
through
which
damaged
organelles
mis-folded
proteins
are
degraded
then
recycled
maintain
homeostasis.
Accumulating
evidence
has
shown
that
impaired
autophagy
contributes
pathogenesis.
In
present
review,
we
highlight
role
autophagy,
bulk
selective
regulating
metabolic
circuits
We
discuss
potential
future
perspectives
autophagy-inducing
strategies
therapeutics.
Cell,
Год журнала:
2022,
Номер
185(22), С. 4135 - 4152.e22
Опубликована: Окт. 1, 2022
Recent
studies
have
begun
to
reveal
critical
roles
for
the
brain's
professional
phagocytes,
microglia,
and
their
receptors
in
control
of
neurotoxic
amyloid
beta
(Aβ)
myelin
debris
accumulation
neurodegenerative
disease.
However,
intracellular
molecules
that
orchestrate
neuroprotective
functions
microglia
remain
poorly
understood.
In
our
studies,
we
find
targeted
deletion
SYK
leads
exacerbated
Aβ
deposition,
aggravated
neuropathology,
cognitive
defects
5xFAD
mouse
model
Alzheimer's
disease
(AD).
Disruption
signaling
this
AD
was
further
shown
impede
development
disease-associated
(DAM),
alter
AKT/GSK3β-signaling,
restrict
phagocytosis
by
microglia.
Conversely,
receptor-mediated
activation
limits
load.
We
also
found
critically
regulates
microglial
DAM
acquisition
demyelinating
Collectively,
these
results
broaden
understanding
key
innate
immune
instruct
beneficial
response
material.
Contemporary
studies
have
completely
changed
the
view
of
brain
immunity
from
envisioning
as
isolated
and
inaccessible
to
peripheral
immune
cells
an
organ
in
close
physical
functional
communication
with
system
for
its
maintenance,
function,
repair.
Circulating
reside
special
niches
brain's
borders,
choroid
plexus,
meninges,
perivascular
spaces,
which
they
patrol
sense
a
remote
manner.
These
niches,
together
meningeal
lymphatic
skull
microchannels,
provide
multiple
routes
interaction
between
system,
addition
blood
vasculature.
In
this
Review,
we
describe
current
ideas
about
their
implications
aging,
diseases,
immune-based
therapeutic
approaches.
