Cellular Signalling,
Год журнала:
2020,
Номер
72, С. 109636 - 109636
Опубликована: Апрель 11, 2020
The
Wnt
signaling
pathway
is
a
crucial
regulator
of
the
intestinal
epithelium
homeostasis
and
altered
in
most
colon
cancers.
While
role
aberrant
canonical,
β-catenin-dependent
has
been
well
established
cancer
promotion,
much
less
known
about
played
by
noncanonical,
β-catenin-independent
this
type
cancer.
This
work
aimed
to
characterize
noncanonical
signal
transduction
cells.
To
end,
we
used
prototype
ligand,
Wnt5a,
comparison
with
Wnt3a,
canonical
β-catenin
activating
ligand.
analysis
expression
profile
receptors
cell
lines
showed
clear
increase
both
level
variety
Frizzled
receptor
types
expressed
cells
compared
non-malignant
We
found
that
Wnt5a
activates
typical
Wnt/Ca++
-
malignant
cells,
inducing
hyperphosphorylation
Dvl1,
Dvl2
Dvl3,
promoting
Ca++
mobilization
as
result
phospholipase
C
(PLC)
activation
via
pertussis
toxin-sensitive
G-protein,
PLC-dependent
migration.
also
while
co-receptor
Ror2
tyrosine
kinase
activity
not
required
for
mobilization-induced
it
inhibitory
effects
on
transcriptional
activity.
Unexpectedly,
although
Wnt3a
ligand
was
unique
stimulating
activity,
simultaneously
activated
PLC,
promoted
mobilization,
induced
Rho
Our
data
indicate,
therefore,
can
activate
at
same
time
so-called
pathways
formation
complex
networks
integrate
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Янв. 3, 2022
Abstract
The
Wnt/β-catenin
pathway
comprises
a
family
of
proteins
that
play
critical
roles
in
embryonic
development
and
adult
tissue
homeostasis.
deregulation
signalling
often
leads
to
various
serious
diseases,
including
cancer
non-cancer
diseases.
Although
many
articles
have
reviewed
from
aspects,
systematic
review
encompassing
the
origin,
composition,
function,
clinical
trials
tumour
diseases
is
lacking.
In
this
article,
we
comprehensively
above
five
aspects
combination
with
latest
research.
Finally,
propose
challenges
opportunities
for
small-molecular
compounds
targeting
Wnt
disease
treatment.
Annual Review of Cell and Developmental Biology,
Год журнала:
2019,
Номер
35(1), С. 591 - 613
Опубликована: Июль 12, 2019
The
vertebrate
vasculature
displays
high
organotypic
specialization,
with
the
structure
and
function
of
blood
vessels
catering
to
specific
needs
each
tissue.
A
unique
feature
central
nervous
system
(CNS)
is
blood-brain
barrier
(BBB).
BBB
regulates
substance
influx
efflux
maintain
a
homeostatic
environment
for
proper
brain
function.
Here,
we
review
development
cell
biology
BBB,
focusing
on
cellular
molecular
regulation
formation
maintenance
through
adulthood.
We
summarize
features
CNS
endothelial
cells
highlight
recent
progress
in
general
principles
regulation.
Finally,
illustrate
why
mechanistic
understanding
could
provide
novel
therapeutic
opportunities
drug
delivery.
Annual Review of Biochemistry,
Год журнала:
2022,
Номер
91(1), С. 571 - 598
Опубликована: Март 19, 2022
The
Wnt
pathway
is
central
to
a
host
of
developmental
and
disease-related
processes.
remarkable
conservation
this
intercellular
signaling
cascade
throughout
metazoan
lineages
indicates
that
it
coevolved
with
multicellularity
regulate
the
generation
spatial
arrangement
distinct
cell
types.
By
regulating
fate
specification,
mitotic
activity,
polarity,
orchestrates
development
tissue
homeostasis,
its
dysregulation
implicated
in
defects,
cancer,
degenerative
disorders.
We
review
advances
our
understanding
key
pathway,
from
protein
production
secretion
relay
signal
cytoplasm
receiving
cell.
discuss
evolutionary
history
as
well
endogenous
synthetic
modulators
activity.
Finally,
we
highlight
remaining
gaps
knowledge
transduction
avenues
for
future
research.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Апрель 7, 2022
It
has
been
noticed
in
recent
years
that
the
unfavorable
effects
of
gut
microbiota
could
exhaust
host
vigor
and
life,
yet
knowledge
theory
are
just
beginning
to
be
established.
Increasing
documentation
suggests
microbiota–gut–brain
axis
not
only
impacts
brain
cognition
psychiatric
symptoms
but
also
precipitates
neurodegenerative
diseases,
such
as
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
multiple
sclerosis
(MS).
How
blood–brain
barrier
(BBB),
a
machinery
protecting
central
nervous
system
(CNS)
from
systemic
circulation,
allows
risky
factors
derived
translocated
into
seems
paradoxical.
For
unique
anatomical,
histological,
immunological
properties
underpinning
its
permeable
dynamics,
BBB
regarded
biomarker
associated
with
neural
pathogenesis.
The
permeability
mice
rats
caused
by
GM
dysbiosis
raises
question
how
metabolites
change
causes
pathophysiology
neuroinflammation
neurodegeneration
(NF&ND)
aging,
pivotal
multidisciplinary
field
tightly
immune
chronic
inflammation.
If
all,
microbiota-induced
inflammation
(GM-SCI)
mainly
refers
excessive
mucosal
immunity
dysregulation,
which
is
often
influenced
dietary
components
age,
produced
at
interface
intestinal
(IB)
or
exacerbated
after
IB
disruption,
initiates
various
common
diseases
along
dispersal
routes,
eventually
impairs
integrity
cause
NF&ND
aging.
To
illustrate
roles
affected
inflammatory
“leaky”
resulting
their
metabolites,
we
reviewed
selected
publications,
including
role
barrier,
influences
on
permeability,
NF&ND,
add
depth
bridging
inflammation,
plausible
mechanism
indispensable
for
corruption
was
highlighted;
namely,
maintenance
cues
cytokines,
may
help
understand
play
major
Chemical Reviews,
Год журнала:
2020,
Номер
121(19), С. 11701 - 11725
Опубликована: Ноя. 9, 2020
During
the
last
three
decades,
a
series
of
key
technological
improvements
turned
atomic
force
microscopy
(AFM)
into
nanoscopic
laboratory
to
directly
observe
and
chemically
characterize
molecular
cell
biological
systems
under
physiological
conditions.
Here,
we
review
that
have
established
AFM
as
an
analytical
tool
quantify
native
from
micro-
nanoscale.
Native
include
living
tissues,
cells,
cellular
components
such
single
or
complexed
proteins,
nucleic
acids,
lipids,
sugars.
We
showcase
procedures
customize
chemical
laboratories
by
functionalizing
tips
outline
advantages
limitations
in
applying
different
modes
image,
sense,
manipulate
biosystems
at
(sub)nanometer
spatial
millisecond
temporal
resolution.
further
discuss
theoretical
approaches
extract
kinetic
thermodynamic
parameters
specific
biomolecular
interactions
detected
for
bonds
extend
discussion
multiple
bonds.
Finally,
highlight
potential
combining
with
optical
spectroscopy
address
full
complexity
tackle
fundamental
challenges
life
sciences.
The
blood-brain
barrier
(BBB)
protects
the
central
nervous
system
(CNS)
from
harmful
blood-borne
factors.
Although
BBB
dysfunction
is
a
hallmark
of
several
neurological
disorders,
therapies
to
restore
function
are
lacking.
An
attractive
strategy
repurpose
developmental
regulators,
such
as
Wnt7a,
into
BBB-protective
agents.
However,
safe
therapeutic
use
Wnt
ligands
complicated
by
their
pleiotropic
Frizzled
signaling
activities.
Taking
advantage
Wnt7a/b-specific
Gpr124/Reck
co-receptor
complex,
we
genetically
engineered
Wnt7a
BBB-specific
activators.
In
“hit-and-run”
adeno-associated
virus–assisted
CNS
gene
delivery
setting,
these
new
Gpr124/Reck-specific
agonists
protected
function,
thereby
mitigating
glioblastoma
expansion
and
ischemic
stroke
infarction.
This
work
reveals
that
specificity
adjustable
defines
modality
treat
disorders
normalizing
BBB.
