Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
Dysregulation
of
epigenetic
mechanisms
plays
a
crucial
role
in
brain
development
and
disease.
Emerging
largely
evidence
suggests
that
Receptor
for
Activated
C-kinase
7
(RACK7),
an
reader
protein,
may
play
neural
developmental
disease,
but
vivo
explorations
are
still
lacking.
Here,
Rack7
conditional
knock-out
mouse
model
is
established
shows
Rack7-deficient
mice
exhibit
overt
defects
associated
with
aberrant
astrocyte
development.
Mechanistically,
it
found
RACK7
interacts
the
histone
H3
lysine
27
(H3K27)
methyltransferase,
i.e.,
Polycomb
Repressive
Complex
2
(PRC2)
complex,
to
establish
genomic
locations
Suppressor
Zeste
12
homolog
(SUZ12)
H3K27
methylation.
Deletion
astrocytes
leads
remarkable
decrease
H3K27me3
chromatin
localization
genome-wide.
Furthermore,
works
together
prevent
overactivation
Wnt
signaling
pathway
other
differentiation
genes
found.
Collectively,
this
study
provides
new
insights
into
cellular
molecular
underlying
regulated
by
RACK7.
Cellular and Molecular Life Sciences,
Год журнала:
2024,
Номер
81(1)
Опубликована: Март 13, 2024
Abstract
The
discoveries
that
cerebrospinal
fluid
participates
in
metabolic
perivascular
exchange
with
the
brain
and
further
drains
solutes
to
meningeal
lymphatic
vessels
have
sparked
a
tremendous
interest
translating
these
seminal
findings
from
animals
humans.
A
potential
two-way
coupling
between
extra-vascular
compartment
peripheral
immune
system
has
implications
exceed
those
concerning
neurodegenerative
diseases,
but
also
imply
central
nervous
pushed
its
immunological
borders
toward
periphery,
where
cross-talk
mediated
by
may
play
role
range
of
neoplastic
diseases.
Due
non-invasive
approach,
magnetic
resonance
imaging
typically
been
preferred
methodology
attempts
image
glymphatic
lymphatics
Even
if
flourishing,
research
field
is
still
cradle,
interpretations
topographically
associate
reports
yet
seemed
downplay
presence
previously
described
anatomical
constituents,
particularly
dura.
In
this
brief
review,
we
illuminate
challenges
assess
evidence
for
glymphatic-lymphatic
coupling.
Finally,
provide
new
perspective
on
how
human
clearance
function
possibly
be
measured
future.
Nature,
Год журнала:
2024,
Номер
628(8009), С. 863 - 871
Опубликована: Апрель 3, 2024
Abstract
Vertebrate
organs
require
locally
adapted
blood
vessels
1,2
.
The
gain
of
such
organotypic
vessel
specializations
is
often
deemed
to
be
molecularly
unrelated
the
process
organ
vascularization.
Here,
opposing
this
model,
we
reveal
a
molecular
mechanism
for
brain-specific
angiogenesis
that
operates
under
control
Wnt7a/b
ligands—well-known
blood–brain
barrier
maturation
signals
3–5
relies
on
Wnt7a/b-dependent
expression
Mmp25,
which
find
enriched
in
brain
endothelial
cells.
CRISPR–Cas9
mutagenesis
zebrafish
reveals
poorly
characterized
glycosylphosphatidylinositol-anchored
matrix
metalloproteinase
selectively
required
tip
cells
enable
their
initial
migration
across
pial
basement
membrane
lining
surface.
Mechanistically,
Mmp25
confers
invasive
competence
by
cleaving
meningeal
fibroblast-derived
collagen
IV
α5/6
chains
within
short
non-collagenous
region
central
helical
part
heterotrimer.
After
genetic
interference
with
composition,
Wnt–β-catenin-dependent
lost,
resulting
properly
patterned,
yet
blood–brain-barrier-defective
cerebrovasculatures.
We
an
organ-specific
mechanism,
shed
light
cell
mechanistic
angiodiversity
and
thereby
illustrate
how
organs,
imposing
local
constraints
angiogenic
cells,
can
select
matching
distinctive
physiological
requirements.
Cellular and Molecular Life Sciences,
Год журнала:
2024,
Номер
81(1)
Опубликована: Май 27, 2024
Abstract
The
brain’s
network
of
perivascular
channels
for
clearance
excess
fluids
and
waste
plays
a
critical
role
in
the
pathogenesis
several
neurodegenerative
diseases
including
cerebral
amyloid
angiopathy
(CAA).
CAA
is
main
cause
hemorrhagic
stroke
elderly,
most
common
vascular
comorbidity
Alzheimer’s
disease
also
implicated
adverse
events
related
to
anti-amyloid
immunotherapy.
Remarkably,
mechanisms
governing
soluble
β—a
key
culprit
CAA—from
brain
draining
lymphatics
systemic
circulation
remains
poorly
understood.
This
knowledge
gap
critically
important
bridge
understanding
pathophysiology
accelerate
development
targeted
therapeutics.
authors
this
review
recently
converged
their
diverse
expertise
field
physiology
specifically
address
problem
within
framework
Leducq
Foundation
Transatlantic
Network
Excellence
on
Brain
Clearance.
discusses
overarching
goal
consortium
explores
evidence
supporting
or
refuting
impaired
with
focus
translating
observations
from
rodents
humans.
We
discuss
anatomical
features
as
well
biophysical
characteristics
fluid
solute
transport.
Trends in Molecular Medicine,
Год журнала:
2024,
Номер
30(3), С. 223 - 238
Опубликована: Янв. 25, 2024
Stem
cell
therapy
is
an
emerging
treatment
paradigm
for
stroke
patients
with
remaining
neurological
deficits.
While
allogeneic
transplants
overcome
the
manufacturing
constraints
of
autologous
grafts,
they
can
be
rejected
by
recipient's
immune
system,
which
identifies
foreign
cells
through
human
leukocyte
antigen
(HLA)
system.
The
heterogeneity
HLA
molecules
in
population
would
require
a
very
high
number
lines,
may
still
inadequate
rare
genetic
HLAs.
Here,
we
outline
key
progress
engineering
pluripotent
stem
and
derived
to
evade
host's
reducing
lines
required,
examine
safety
measures
explored
both
preclinical
studies
upcoming
clinical
trials.
Neurobiology of Disease,
Год журнала:
2025,
Номер
205, С. 106791 - 106791
Опубликована: Янв. 6, 2025
Neurodegenerative
diseases
(ND)
are
characterized
by
the
accumulation
of
aggregated
proteins.
The
glymphatic
system,
through
its
rapid
exchange
mechanisms
between
cerebrospinal
fluid
(CSF)
and
interstitial
(ISF),
facilitates
movement
metabolic
substances
within
brain,
serving
functions
akin
to
those
peripheral
lymphatic
system.
This
emerging
waste
clearance
mechanism
offers
a
novel
perspective
on
removal
pathological
in
ND.
article
elucidates
recent
discoveries
regarding
system
updates
relevant
concepts
model.
It
discusses
potential
roles
ND,
including
Alzheimer's
disease
(AD),
Parkinson's
(PD),
multiple
atrophy
(MSA),
proposes
as
therapeutic
target
for
these
conditions.
Alzheimer s Research & Therapy,
Год журнала:
2025,
Номер
17(1)
Опубликована: Янв. 31, 2025
The
emerging
evidence
of
the
role
glymphatic
system
(GS)
in
Alzheimer's
disease
(AD)
provides
new
opportunities
for
intervention
from
earliest
stages
disease.
aim
study
is
to
evaluate
efficacy
GS
AD
identify
biomarkers.
We
performed
a
two-stage
proteomic
health
using
intravenous
gadolinium-based
contrast
agent
(GBCA)
with
serial
T1
3T
magnetic
resonance
imaging
(MRI)
individuals
amnestic
mild
cognitive
impairment
(aMCI).
In
Stage
1
(evaluated
Cohort
aMCI
participants
(n
=
11)),
we
correlated
levels
7K
cerebrospinal
fluid
(CSF)
proteins
(estimated
by
SOMAscan)
78
Freesurfer-segmented
brain
regions
interest
(ROIs).
A
total
seven
different
were
significantly
associated
(p-value
<
6.4
×
10-4).
stronger
correlations
identified
NSUN6,
GRAAK,
OLFML3,
ACTN2,
RUXF,
SHPS1
and
TIM-4.
pathway
enrichment
analysis
revealed
that
mainly
implicated
neurodegenerative
processes,
immunity
inflammation.
2,
validated
these
results
cohort
(with
without
pathology
CSF
(aMCI(-)
aMCI/AD(
+);
n
22
7,
respectively)
healthy
controls
10).
Proteomic
prediction
models
generated
each
ROI.
These
compared
demographic-only
identifying
aMCI(-)
+)
vs
controls.
This
was
repeated
determine
if
could
those
both
found
outperform
models.
Our
identifies
linked
involved
immune
participants.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 27, 2024
Abstract
Spinal
cord
injury
(SCI)
leads
to
fibrotic
scar
formation
at
the
lesion
site,
yet
heterogeneity
of
remains
elusive.
Here
we
show
in
distribution,
origin,
and
function
fibroblasts
within
scars
after
SCI
mice
female
monkeys.
Utilizing
lineage
tracing
single-cell
RNA
sequencing
(scRNA-seq),
found
that
perivascular
(PFs),
meningeal
(MFs),
rather
than
pericytes/vascular
smooth
cells
(vSMCs),
primarily
contribute
both
transection
crush
SCI.
Crabp2
+
/Emb+
(CE-F)
derived
from
meninges
localize
central
region
scars,
demonstrating
enhanced
cholesterol
synthesis
secretion
type
I
collagen
fibronectin.
In
contrast,
perivascular/pial
Lama1
/Lama2+
(LA-F)
are
predominantly
periphery
lesion,
expressing
laminin
IV
functionally
involved
angiogenesis
lipid
transport.
These
findings
may
provide
a
comprehensive
understanding
for
remodeling
heterogeneous
