Advanced Drug Delivery Reviews,
Journal Year:
2023,
Volume and Issue:
197, P. 114820 - 114820
Published: April 11, 2023
The
blood–brain
barrier
(BBB)
is
a
highly
regulated
physical
and
functional
boundary
that
tightly
controls
the
transport
of
materials
between
blood
brain.
There
an
increasing
recognition
BBB
dysfunctional
in
wide
range
neurological
disorders;
this
dysfunction
can
be
symptomatic
disease
but
also
play
role
etiology.
exploited
for
delivery
therapeutic
nanomaterials.
For
example,
there
transient,
disruption
diseases
such
as
brain
injury
stroke,
which
allows
temporary
access
nanomaterials
into
Physical
through
external
energy
sources
now
being
clinically
pursued
to
increase
In
other
diseases,
takes
on
new
properties
leveraged
by
carriers.
instance,
neuroinflammation
induces
expression
receptors
targeted
ligand-modified
nanomaterials,
endogenous
homing
immune
cells
diseased
hijacked
Lastly,
pathways
altered
nanomaterial
transport.
review,
we
will
describe
changes
occur
disease,
how
these
have
been
engineered
increased
Cell,
Journal Year:
2023,
Volume and Issue:
186(20), P. 4386 - 4403.e29
Published: Sept. 1, 2023
Altered
microglial
states
affect
neuroinflammation,
neurodegeneration,
and
disease
but
remain
poorly
understood.
Here,
we
report
194,000
single-nucleus
transcriptomes
epigenomes
across
443
human
subjects
diverse
Alzheimer's
(AD)
pathological
phenotypes.
We
annotate
12
transcriptional
states,
including
AD-dysregulated
homeostatic,
inflammatory,
lipid-processing
states.
identify
1,542
AD-differentially-expressed
genes,
both
microglia-state-specific
disease-stage-specific
alterations.
By
integrating
epigenomic,
transcriptomic,
motif
information,
infer
upstream
regulators
of
cell
gene-regulatory
networks,
enhancer-gene
links,
transcription-factor-driven
state
transitions.
demonstrate
that
ectopic
expression
our
predicted
homeostatic-state
activators
induces
homeostatic
features
in
iPSC-derived
microglia-like
cells,
while
inhibiting
inflammation
can
block
inflammatory
progression.
Lastly,
pinpoint
the
AD-risk
genes
differential
their
during
AD
Overall,
provide
insights
underlying
state-specific
AD-stage-specific
alterations
at
unprecedented
resolution.
Molecular Neurodegeneration,
Journal Year:
2023,
Volume and Issue:
18(1)
Published: July 11, 2023
Abstract
Vascular
cognitive
impairment
and
dementia
(VCID)
is
commonly
caused
by
vascular
injuries
in
cerebral
large
small
vessels
a
key
driver
of
age-related
decline.
Severe
VCID
includes
post-stroke
dementia,
subcortical
ischemic
multi-infarct
mixed
dementia.
While
acknowledged
as
the
second
most
common
form
after
Alzheimer’s
disease
(AD)
accounting
for
20%
cases,
AD
frequently
coexist.
In
VCID,
vessel
(cSVD)
often
affects
arterioles,
capillaries,
venules,
where
arteriolosclerosis
amyloid
angiopathy
(CAA)
are
major
pathologies.
White
matter
hyperintensities,
recent
infarcts,
lacunes
presumed
origin,
enlarged
perivascular
space,
microbleeds,
brain
atrophy
neuroimaging
hallmarks
cSVD.
The
current
primary
approach
to
cSVD
treatment
control
risk
factors
such
hypertension,
dyslipidemia,
diabetes,
smoking.
However,
causal
therapeutic
strategies
have
not
been
established
partly
due
heterogeneous
pathogenesis
this
review,
we
summarize
pathophysiology
discuss
probable
etiological
pathways
focusing
on
hypoperfusion/hypoxia,
blood–brain
barriers
(BBB)
dysregulation,
fluid
drainage
disturbances,
inflammation
define
potential
diagnostic
targets
Annual Review of Neuroscience,
Journal Year:
2022,
Volume and Issue:
45(1), P. 447 - 469
Published: April 20, 2022
Recombinant
adeno-associated
viruses
(AAVs)
are
commonly
used
gene
delivery
vehicles
for
neuroscience
research.
They
have
two
engineerable
features:
the
capsid
(outer
protein
shell)
and
cargo
(encapsulated
genome).
These
features
can
be
modified
to
enhance
cell
type
or
tissue
tropism
control
transgene
expression,
respectively.
Several
engineered
AAV
capsids
with
unique
tropisms
been
identified,
including
variants
enhanced
central
nervous
system
transduction,
specificity,
retrograde
transport
in
neurons.
Pairing
these
AAVs
modern
regulatory
elements
state-of-the-art
reporter,
sensor,
effector
enables
highly
specific
expression
anatomical
functional
analyses
of
brain
cells
circuits.
Here,
we
discuss
recent
advances
that
provide
a
comprehensive
(capsid
cargo)
toolkit
genetic
access
molecularly
defined
types.
Cell,
Journal Year:
2022,
Volume and Issue:
185(20), P. 3753 - 3769.e18
Published: Sept. 1, 2022
Interactions
between
angiogenesis
and
neurogenesis
regulate
embryonic
brain
development.
However,
a
comprehensive
understanding
of
the
stages
vascular
cell
maturation
is
lacking,
especially
in
prenatal
human
brain.
Using
fluorescence-activated
sorting,
single-cell
transcriptomics,
histological
ultrastructural
analyses,
we
show
that
an
ensemble
endothelial
mural
subtypes
tile
vasculature
during
second
trimester.
These
cells
follow
distinct
developmental
trajectories
utilize
diverse
signaling
mechanisms,
including
collagen,
laminin,
midkine,
to
facilitate
cell-cell
communication
maturation.
Interestingly,
our
results
reveal
tip
cells,
subtype
are
highly
enriched
near
ventricular
zone,
site
active
neurogenesis.
Consistent
with
these
observations,
transplanted
into
cortical
organoids
exhibit
restricted
lineage
potential
favors
promotes
neurogenesis,
reduces
cellular
stress.
Together,
uncover
important
mechanisms
this
critical
period
Nature Aging,
Journal Year:
2024,
Volume and Issue:
4(1), P. 33 - 47
Published: Jan. 9, 2024
Abstract
Alzheimer’s
disease
(AD)
is
heterogenous
at
the
molecular
level.
Understanding
this
heterogeneity
critical
for
AD
drug
development.
Here
we
define
subtypes
using
mass
spectrometry
proteomics
in
cerebrospinal
fluid,
based
on
1,058
proteins,
with
different
levels
individuals
(
n
=
419)
compared
to
controls
187).
These
had
alterations
protein
that
were
associated
distinct
processes:
subtype
1
was
characterized
by
proteins
related
neuronal
hyperplasticity;
2
innate
immune
activation;
3
RNA
dysregulation;
4
choroid
plexus
dysfunction;
and
5
blood–brain
barrier
impairment.
Each
specific
genetic
risk
variants,
example,
enriched
TREM2
R47H.
Subtypes
also
differed
clinical
outcomes,
survival
times
anatomical
patterns
of
brain
atrophy.
results
indicate
highlight
need
personalized
medicine.
Stroke,
Journal Year:
2023,
Volume and Issue:
54(6)
Published: April 3, 2023
Preservation
of
brain
health
has
emerged
as
a
leading
public
priority
for
the
aging
world
population.
Advances
in
neurovascular
biology
have
revealed
an
intricate
relationship
among
cells,
meninges,
and
hematic
lymphatic
vasculature
(the
neurovasculome)
that
is
highly
relevant
to
maintenance
cognitive
function.
In
this
scientific
statement,
multidisciplinary
team
experts
examines
these
advances,
assesses
their
relevance
disease,
identifies
knowledge
gaps,
provides
future
directions.
