Journal of Neuroscience,
Год журнала:
2023,
Номер
43(25), С. 4725 - 4737
Опубликована: Май 19, 2023
Aging
is
a
significant
risk
factor
associated
with
the
progression
of
CNS
neurodegenerative
diseases
including
multiple
sclerosis
(MS).
Microglia,
resident
macrophages
parenchyma,
are
major
population
immune
cells
that
accumulate
in
MS
lesions.
While
they
normally
regulate
tissue
homeostasis
and
facilitate
clearance
neurotoxic
molecules
oxidized
phosphatidylcholines
(OxPCs),
their
transcriptome
neuroprotective
functions
reprogrammed
by
aging.
Thus,
determining
factors
instigate
aging
microglia
dysfunction
can
lead
to
new
insights
for
promoting
repair
halting
disease
progression.
Through
single-cell
RNA
sequencing
(scRNAseq),
we
identified
Lgals3,
which
encodes
galectin-3
(Gal3),
as
an
age
upregulated
gene
responding
OxPC.
Consistently,
excess
Gal3
accumulated
OxPC
lysolecithin-induced
focal
spinal
cord
white
matter
(SCWM)
lesions
middle-aged
mice
compared
young
mice.
was
also
elevated
mouse
experimental
autoimmune
encephalomyelitis
(EAE)
more
importantly
brain
from
two
male
one
female
individuals.
delivery
alone
into
did
not
induce
damage,
its
co-delivery
increased
cleaved
caspase
3
IL-1β
within
exacerbated
OxPC-induced
injury.
Conversely,
OxPC-mediated
neurodegeneration
reduced
Gal3-/-
Gal3+/+
neuroinflammation
overexpression
microglia/macrophages
may
be
detrimental
CNS.SIGNIFICANCE
STATEMENT
accelerates
such
Understanding
molecular
mechanisms
increases
susceptibility
damage
could
strategies
manage
Here,
highlight
microglia/macrophage-associated
(Gal3)
More
importantly,
co-injection
lipids
found
lesions,
caused
greater
injection
alone,
whereas
genetic
loss
damage.
These
results
demonstrate
suggest
deposition
contribute
neurodegeneration.
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
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.
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
221(3)
Опубликована: Янв. 30, 2024
Outer
retinal
degenerations,
including
age-related
macular
degeneration
(AMD),
are
characterized
by
photoreceptor
and
pigment
epithelium
(RPE)
atrophy.
In
these
blinding
diseases,
macrophages
accumulate
at
atrophic
sites,
but
their
ontogeny
niche
specialization
remain
poorly
understood,
especially
in
humans.
We
uncovered
a
unique
profile
of
microglia,
marked
galectin-3
upregulation,
sites
mouse
models
human
AMD.
disease
models,
conditional
deletion
microglia
led
to
phagocytosis
defects
consequent
augmented
death,
RPE
damage,
vision
loss,
indicating
protective
roles.
Mechanistically,
Trem2
signaling
orchestrated
microglial
migration
induced
expression.
Moreover,
pharmacologic
agonization
heightened
protection
galectin-3–dependent
manner.
elderly
subjects,
we
identified
this
highly
conserved
population
that
expressed
Trem2.
This
was
significantly
enriched
the
RPE-choroid
AMD
subjects.
Collectively,
our
findings
reveal
neuroprotective
potential
therapeutic
target
for
mitigating
degeneration.
Journal of Neuroimmunology,
Год журнала:
2024,
Номер
390, С. 578342 - 578342
Опубликована: Апрель 5, 2024
Alzheimer's
disease
(AD)
is
a
neurodegenerative
characterized
by
cognitive
decline
that
severely
affects
patients
and
their
families.
Genetic
environmental
risk
factors,
such
as
viral
infections,
synergize
to
accelerate
the
aging-associated
neurodegeneration.
factors
for
late-onset
AD
(LOAD),
which
accounts
most
cases,
are
predominantly
implicated
in
microglial
immune
cell
functions.
As
such,
microglia
play
major
role
amyloid
beta
(Aβ)
plaque
(the
pathological
hallmark
of
AD)
formation.
This
review
aims
provide
an
overview
current
knowledge
regarding
Aβ
formation,
well
impact
on
morphological
functional
diversity
plaques.
Based
this
discussion,
we
seek
identify
challenges
opportunities
field
with
potential
therapeutic
implications.
Annual Review of Immunology,
Год журнала:
2024,
Номер
42(1), С. 585 - 613
Опубликована: Март 1, 2024
Alzheimer
disease
(AD)
is
the
most
common
neurodegenerative
disease,
and
with
no
efficient
curative
treatment
available,
its
medical,
social,
economic
burdens
are
expected
to
dramatically
increase.
AD
historically
characterized
by
amyloid
β
(Aβ)
plaques
tau
neurofibrillary
tangles,
but
over
last
25
years
chronic
immune
activation
has
been
identified
as
an
important
factor
contributing
pathogenesis.
In
this
article,
we
review
recent
advances
in
our
understanding
of
significance
development
AD.
We
describe
how
brain-resident
macrophages,
microglia,
able
detect
Aβ
species
be
activated,
well
consequences
activated
microglia
discuss
transcriptional
changes
AD,
their
unique
heterogeneity
humans,
emerging
strategies
study
human
microglia.
Finally,
expose,
beyond
role
peripheral
signals
different
cell
types
activation.
