Cell,
Год журнала:
2021,
Номер
184(19), С. 5031 - 5052.e26
Опубликована: Сен. 1, 2021
Pancreatic
ductal
adenocarcinoma
(PDAC)
is
a
highly
aggressive
cancer
with
poor
patient
survival.
Toward
understanding
the
underlying
molecular
alterations
that
drive
PDAC
oncogenesis,
we
conducted
comprehensive
proteogenomic
analysis
of
140
pancreatic
cancers,
67
normal
adjacent
tissues,
and
9
tissues.
Proteomic,
phosphoproteomic,
glycoproteomic
analyses
were
used
to
characterize
proteins
their
modifications.
In
addition,
whole-genome
sequencing,
whole-exome
methylation,
RNA
sequencing
(RNA-seq),
microRNA
(miRNA-seq)
performed
on
same
tissues
facilitate
an
integrated
determine
impact
genomic
protein
expression,
signaling
pathways,
post-translational
To
ensure
robust
downstream
analyses,
tumor
neoplastic
cellularity
was
assessed
via
multiple
orthogonal
strategies
using
features
verified
pathological
estimation
based
histological
review.
This
characterization
will
serve
as
valuable
resource
for
community,
paving
way
early
detection
identification
novel
therapeutic
targets.
Physiological Reviews,
Год журнала:
2018,
Номер
99(1), С. 21 - 78
Опубликована: Окт. 3, 2018
The
blood-brain
barrier
(BBB)
prevents
neurotoxic
plasma
components,
blood
cells,
and
pathogens
from
entering
the
brain.
At
same
time,
BBB
regulates
transport
of
molecules
into
out
central
nervous
system
(CNS),
which
maintains
tightly
controlled
chemical
composition
neuronal
milieu
that
is
required
for
proper
functioning.
In
this
review,
we
first
examine
molecular
cellular
mechanisms
underlying
establishment
BBB.
Then,
focus
on
physiology,
endothelial
pericyte
transporters,
perivascular
paravascular
transport.
Next,
discuss
rare
human
monogenic
neurological
disorders
with
primary
genetic
defect
in
BBB-associated
cells
demonstrating
link
between
breakdown
neurodegeneration.
review
effects
genes
inheritance
and/or
increased
susceptibility
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Huntington's
disease,
amyotrophic
lateral
sclerosis
(ALS)
relation
to
other
pathologies
deficits.
We
next
how
dysfunction
relates
deficits
majority
sporadic
AD,
PD,
ALS
cases,
multiple
sclerosis,
neurodegenerative
disorders,
acute
CNS
such
as
stroke,
traumatic
brain
injury,
spinal
cord
epilepsy.
Lastly,
BBB-based
therapeutic
opportunities.
conclude
lessons
learned
future
directions,
emphasis
technological
advances
investigate
functions
living
brain,
at
level,
address
key
unanswered
questions.
Science,
Год журнала:
2018,
Номер
362(6411), С. 181 - 185
Опубликована: Окт. 11, 2018
Glia
constitute
roughly
half
of
the
cells
central
nervous
system
(CNS)
but
were
long-considered
to
be
static
bystanders
its
formation
and
function.
Here
we
provide
an
overview
how
diverse
dynamic
functions
glial
orchestrate
essentially
all
aspects
Radial
glia,
astrocytes,
oligodendrocyte
progenitor
cells,
oligodendrocytes,
microglia
each
influence
development,
from
neuronal
birth,
migration,
axon
specification,
growth
through
circuit
assembly
synaptogenesis.
As
neural
circuits
mature,
distinct
glia
fulfill
key
roles
in
synaptic
communication,
plasticity,
homeostasis,
network-level
activity
monitoring
alteration
CNS
structure
Continued
elucidation
cell
biology,
interactions
neurons
will
enrich
our
understanding
formation,
health,
Fluids and Barriers of the CNS,
Год журнала:
2014,
Номер
11(1), С. 10 - 10
Опубликована: Янв. 1, 2014
According
to
the
traditional
understanding
of
cerebrospinal
fluid
(CSF)
physiology,
majority
CSF
is
produced
by
choroid
plexus,
circulates
through
ventricles,
cisterns,
and
subarachnoid
space
be
absorbed
into
blood
arachnoid
villi.
This
review
surveys
key
developments
leading
concept.
Challenging
this
concept
are
novel
insights
utilizing
molecular
cellular
biology
as
well
neuroimaging,
which
indicate
that
physiology
may
much
more
complex
than
previously
believed.
The
circulation
comprises
not
only
a
directed
flow
CSF,
but
in
addition
pulsatile
fro
movement
throughout
entire
brain
with
local
exchange
between
blood,
interstitial
fluid,
CSF.
Astrocytes,
aquaporins,
other
membrane
transporters
elements
water
homeostasis.
A
continuous
bidirectional
at
barrier
produces
rates,
exceed
choroidal
production
rate
far.
around
vessels
penetrating
from
Virchow
Robin
spaces
provides
both
drainage
pathway
for
clearance
waste
molecules
site
interaction
systemic
immune
system
brain.
Important
physiological
functions,
example
regeneration
during
sleep,
depend
on
circulation.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Май 25, 2023
Abstract
Blood–brain
barrier
(BBB)
is
a
natural
protective
membrane
that
prevents
central
nervous
system
(CNS)
from
toxins
and
pathogens
in
blood.
However,
the
presence
of
BBB
complicates
pharmacotherapy
for
CNS
disorders
as
most
chemical
drugs
biopharmaceuticals
have
been
impeded
to
enter
brain.
Insufficient
drug
delivery
into
brain
leads
low
therapeutic
efficacy
well
aggravated
side
effects
due
accumulation
other
organs
tissues.
Recent
breakthrough
materials
science
nanotechnology
provides
library
advanced
with
customized
structure
property
serving
powerful
toolkit
targeted
delivery.
In-depth
research
field
anatomical
pathological
study
on
further
facilitates
development
brain-targeted
strategies
enhanced
crossing.
In
this
review,
physiological
different
cells
contributing
are
summarized.
Various
emerging
permeability
regulation
crossing
including
passive
transcytosis,
intranasal
administration,
ligands
conjugation,
coating,
stimuli-triggered
disruption,
overcome
obstacle
highlighted.
Versatile
systems
ranging
organic,
inorganic,
biologics-derived
their
synthesis
procedures
unique
physio-chemical
properties
summarized
analyzed.
This
review
aims
provide
an
up-to-date
comprehensive
guideline
researchers
diverse
fields,
offering
perspectives
system.
Neurobiology of Disease,
Год журнала:
2016,
Номер
107, С. 41 - 56
Опубликована: Июль 17, 2016
Alzheimer's
disease
(AD)
is
a
chronic
neurodegenerative
disorder
characterized
by
the
pathological
accumulation
of
amyloid
beta
(Aβ)
peptides
and
neurofibrillary
tangles
containing
hyperphosphorylated
neuronal
tau
protein.
AD
pathology
also
brain
inflammation,
which
promotes
pathogenesis.
In
this
context,
blood-brain
barrier
(BBB),
highly
specialized
endothelial
cell
membrane
that
lines
cerebral
microvessels,
represents
interface
between
neural
cells
circulating
immune
system.
The
BBB
thus
plays
key
role
in
generation
maintenance
inflammation
during
AD.
operates
within
neurovascular
unit
(NVU),
includes
clusters
glial
cells,
neurons
pericytes.
NVU
becomes
dysfunctional
AD,
each
its
components
may
undergo
functional
changes
contribute
to
injury
cognitive
deficit.
transgenic
animals
with
AD-like
pathology,
recent
studies
have
shown
leukocytes
migrate
through
activated
endothelium
when
certain
adhesion
molecules
are
expressed,
penetrating
into
parenchyma,
interacting
potentially
affecting
their
structural
integrity
functionality.
Therefore,
migrating
system
vessels
act
concert
modified
be
integrated
NVU.
Notably,
blocking
mechanisms
controlling
leukocyte-endothelial
interactions
inhibits
both
Aβ
deposition
hyperphosphorylation,
reduces
memory
loss
models.
characterization
molecular
vascular
leukocyte
trafficking
could
therefore
help
determine
basis
dysfunction
lead
development
new
therapeutic
approaches.
Brain Research Bulletin,
Год журнала:
2018,
Номер
143, С. 155 - 170
Опубликована: Окт. 1, 2018
The
acute
or
chronic
drug
treatments
for
different
neurodegenerative
and
psychiatric
disorders
are
challenging
from
several
aspects.
low
bioavailability
limited
brain
exposure
of
oral
drugs,
the
rapid
metabolism,
elimination,
unwanted
side
effects
also
high
dose
to
be
added
mean
both
inconvenience
patients
costs
patients,
their
family
society.
reason
penetration
compounds
is
that
they
have
overcome
blood-brain
barrier
which
protects
against
xenobiotics.
Intranasal
administration
one
promising
options
bypass
barrier,
reduce
systemic
adverse
drugs
lower
doses
administered.
Furthermore,
administered
using
nasal
route
usually
higher
bioavailability,
less
result
in
at
similar
dosage
than
drugs.
In
this
review
focus
on
giving
an
overview
anatomical
cellular
structure
cavity
absorption
surface.
It
presents
some
possibilities
enhance
through
summarizes
vitro,
ex
vivo
technologies
test
delivery
across
epithelium
into
brain.
Finally,
authors
give
a
critical
evaluation
showing
its
main
advantages
limitations
CNS
targeting.
Frontiers in Neuroengineering,
Год журнала:
2013,
Номер
6
Опубликована: Янв. 1, 2013
It
has
been
more
than
100
years
since
Paul
Ehrlich
reported
that
various
water-soluble
dyes
injected
into
the
circulation
did
not
enter
brain.
Since
Ehrlich's
first
experiments,
only
a
small
number
of
molecules,
such
as
alcohol
and
caffeine
have
found
to
cross
blood-brain
barrier,
this
selective
permeability
remains
major
roadblock
treatment
many
central
nervous
system
diseases.
At
same
time,
diseases
are
associated
with
disruption
barrier
can
lead
changes
in
permeability,
modulation
immune
cell
transport,
trafficking
pathogens
Therefore,
advances
our
understanding
structure
function
key
developing
effective
treatments
for
wide
range
Over
past
10
it
become
recognized
is
complex,
dynamic
involves
biomechanical
biochemical
signaling
between
vascular
Here
we
reconstruct
structure,
function,
transport
properties
from
an
engineering
perspective.
New
insight
physics
could
ultimately
clinical
