Biomaterials Science,
Journal Year:
2023,
Volume and Issue:
12(3), P. 710 - 724
Published: Dec. 5, 2023
Immune
cells
are
the
housekeepers
of
human
body.
They
protect
body
from
pathogens,
cellular
damage,
and
foreign
matter.
Proper
activation
immune
is
great
significance
to
diseases
such
as
infection,
inflammation,
neurodegeneration.
However,
excessive
can
be
detrimental.
An
ideal
biomaterial
could
enhance
function
without
proinflammation.
In
this
work,
we
used
sporopollenin
exine
capsules
(SEC)
pollen
promote
functions
primary
microglia,
a
typical
resident
cell
brain.
We
found
that
microglia
aggregated
around
SEC
did
not
undergo
any
improved
viability,
migration,
phagocytosis,
anti-inflammatory
ability
microglia.
By
exploring
underlying
mechanism
microglial
production
cytotoxic
pro-inflammatory
cytokines,
protects
against
inflammation
induced
by
lipopolysaccharide
(LPS),
an
immunostimulatory
factor,
through
toll-like
receptor
4
(TLR4)
signaling
pathway
in
myeloid
differentiation
factor
88-dependent
manner.
These
findings
might
shed
light
on
potential
application
transplantation
for
treatment
microglia-associated
degenerative
central
nervous
system
diseases.
Neuron,
Journal Year:
2024,
Volume and Issue:
112(16), P. 2686 - 2707.e8
Published: June 18, 2024
Microglia
replacement
strategies
are
increasingly
being
considered
for
the
treatment
of
primary
microgliopathies
like
adult-onset
leukoencephalopathy
with
axonal
spheroids
and
pigmented
glia
(ALSP).
However,
available
mouse
models
fail
to
recapitulate
diverse
neuropathologies
reduced
microglia
numbers
observed
in
patients.
In
this
study,
we
generated
a
xenotolerant
model
lacking
fms-intronic
regulatory
element
(FIRE)
enhancer
within
Csf1r,
which
develops
nearly
all
hallmark
pathologies
associated
ALSP.
Remarkably,
transplantation
human
induced
pluripotent
stem
cell
(iPSC)-derived
microglial
(iMG)
progenitors
restores
homeostatic
signature
prevents
development
spheroids,
white
matter
abnormalities,
reactive
astrocytosis,
brain
calcifications.
Furthermore,
CRISPR-corrected
ALSP-patient-derived
iMG
reverses
pre-existing
astrogliosis,
calcification
pathologies.
Together
accompanying
study
by
Munro
colleagues,
our
results
demonstrate
utility
FIRE
mice
ALSP
provide
compelling
evidence
that
could
offer
promising
new
therapeutic
strategy
perhaps
other
microglia-associated
neurological
disorders.
Molecular Neurodegeneration,
Journal Year:
2024,
Volume and Issue:
19(1)
Published: April 5, 2024
Abstract
Background
Induced
pluripotent
stem
cell-derived
microglia
(iMGL)
represent
an
excellent
tool
in
studying
microglial
function
health
and
disease.
Yet,
since
differentiation
survival
of
iMGL
are
highly
reliant
on
colony-stimulating
factor
1
receptor
(CSF1R)
signaling,
it
is
difficult
to
use
study
dysfunction
associated
with
pathogenic
defects
CSF1R.
Methods
Serial
modifications
existing
protocol
were
made,
including
but
not
limited
changes
growth
combination
drive
differentiation,
until
successful
derivation
microglia-like
cells
from
adult-onset
leukoencephalopathy
axonal
spheroids
pigmented
glia
(ALSP)
patient
carrying
a
c.2350G
>
A
(p.V784M)
CSF1R
variant.
Using
healthy
control
lines,
the
quality
new
was
validated
through
cell
yield
assessment,
measurement
marker
expression,
transcriptomic
comparison
primary
microglia,
evaluation
inflammatory
phagocytic
activities.
Similarly,
molecular
functional
characterization
ALSP
patient-derived
carried
out
iMGL.
Results
The
newly
devised
allowed
generation
enhanced
similarity
cultured
human
higher
scavenging
competence
at
~
threefold
greater
compared
original
protocol.
this
protocol,
decreased
autophosphorylation
surface
expression
observed
derived
those
controls.
Additionally,
presented
migratory
defect
accompanying
temporal
reduction
purinergic
P2Y12
(
P2RY12
)
heightened
capacity
internalize
myelin,
as
well
response
Pam
3
CSK
4
.
Poor
confirmed
be
consequence
haploinsufficiency,
feature
also
following
knockdown
or
inhibition
mature
iMGL,
WT/KO
WT/E633K
their
respective
isogenic
Conclusions
We
optimized
pre-existing
generating
powerful
involvement
neurological
diseases.
we
have
generated
for
first
time
variant,
preliminary
pointing
toward
alterations
migratory,
Graphical
Alzheimer s Research & Therapy,
Journal Year:
2025,
Volume and Issue:
17(1)
Published: April 3, 2025
Abstract
Background
Ethnic
variations
and
detection
methods
may
lead
to
differences
in
diagnostic
biomarkers
of
dementia,
few
comparative
studies
have
evaluated
the
six
plasma
Alzheimer’s
disease
(AD)
other
neurodegenerative
dementias
Chinese
population.
Methods
A
cross-sectional
cohort
668
participants
were
enrolled,
including
245
amnesic
mild
cognitive
impairment
(aMCI)
or
AD
patients
with
Aβ
positive
pathology,
67
frontotemporal
dementia
(FTD),
100
progressive
supranuclear
palsy
(PSP),
72
Lewy
bodies
(DLB)
184
healthy
controls.
Additionally,
a
longitudinal
subset
19
aMCI
30
was
followed
for
an
average
period
1
year.
Plasma
biomarkers,
p-tau181,
p-tau217,
p-tau231,
NfL,
GFAP,
α-synuclein,
simultaneously
measured
using
novel
single
molecular
array
method.
Aβ42
p-tau181
levels
CSF,
amyloid
PET
structural
MRI
measured.
Results
p-tau217
p-tau231
most
effective
diagnosing
aMCI/AD
(AUC
=
0.95
0.93,
respectively),
while
presented
best
differential
diagnosis
from
PSP,
FTD
DLB
respectively
0.84,
0.81
0.83).
α-synuclein
as
biomarker
PSP
variant
behavior
subtypes
0.74,
respectively).
Among
them,
GFAP
a-synuclein
negatively
correlated
CSF
Aβ42/40,
positively
p-tau181.
Besides,
associated
temporal
lobe
volume,
frontal
volume.
Longitudinal
analysis
showed
higher
could
predict
decline
progression.
Conclusions
This
study
validate
practicality
blood
Han
population
molecule
immune
Through
clinical
performance
several
we
found
diagnosis,
p-tau
high
accuracy
is
multiple
aspects
can
reflect
dynamic
AD.
Frontiers in Cellular Neuroscience,
Journal Year:
2023,
Volume and Issue:
17
Published: Oct. 30, 2023
Recent
studies
have
emphasized
the
role
of
microglia
in
progression
many
neurodegenerative
diseases.
The
colony
stimulating
factors,
CSF-1
(M-CSF),
granulocyte-macrophage
CSF
(GM-CSF)
and
granulocyte
(G-CSF)
regulate
through
different
cognate
receptors.
While
receptors
for
GM-CSF
(GM-CSFR)
G-CSF
(G-CSFR)
are
specific
their
ligands,
shares
its
receptor,
receptor-tyrosine
kinase
(CSF-1R),
with
interleukin-34
(IL-34).
All
four
cytokines
expressed
locally
CNS.
Activation
CSF-1R
macrophages
is
anti-inflammatory.
In
contrast,
actions
elicit
activated
states.
We
here
review
roles
each
these
CNS
how
they
contribute
to
development
disease
a
mouse
model
CSF-1R-related
leukodystrophy.
Understanding
this
may
illuminate
contribution
or
exacerbation
other
Glia,
Journal Year:
2023,
Volume and Issue:
71(11), P. 2664 - 2678
Published: July 30, 2023
Abstract
Mutations
leading
to
colony‐stimulating
factor‐1
receptor
(
CSF‐1R
)
loss‐of‐function
or
haploinsufficiency
cause
CSF1R‐related
leukoencephalopathy
(CRL),
an
adult‐onset
disease
characterized
by
loss
of
myelin
and
neurodegeneration,
for
which
there
is
no
effective
therapy.
Symptom
onset
usually
occurs
in
the
fourth
decade
life
penetrance
carriers
high.
However,
familial
studies
have
identified
a
few
pathogenic
CSF1R
mutations
that
remain
asymptomatic
even
their
seventh
life,
raising
possibility
development
severity
might
be
influenced
environmental
factors.
Here
we
report
new
cases
long‐term
glucocorticoid
treatment
associated
with
status
elder
mutations.
The
main
objective
present
study
was
investigate
link
between
chronic
immunosuppression
initiated
pre‐symptomatically
resistance
symptomatic
CRL,
Csf1r
+/−
mouse
model.
We
show
prednisone
administration
prevents
memory,
motor
coordination
social
interaction
deficits,
as
well
demyelination,
neurodegeneration
microgliosis
these
deficits.
These
findings
are
agreement
preliminary
clinical
observations
support
concept
pre‐symptomatic
protective
patients
carrying
variants
CRL.
Proteomic
analysis
microglia
oligodendrocytes
indicates
suppresses
processes
involved
microglial
activation
alleviates
senescence
improves
fitness
oligodendrocytes.
This
also
identifies
potential
targets
therapeutic
intervention.
