Experimental & Molecular Medicine,
Год журнала:
2024,
Номер
56(5), С. 1206 - 1220
Опубликована: Май 17, 2024
Abstract
The
etiology
of
preeclampsia
(PE),
a
severe
complication
pregnancy
with
several
clinical
manifestations
and
high
incidence
maternal
fetal
morbidity
mortality,
remains
unclear.
This
issue
is
major
hurdle
for
effective
treatment
strategies.
We
recently
demonstrated
that
PE
exhibits
an
Alzheimer-like
impaired
autophagy
proteinopathy
in
the
placenta.
Targeting
these
pathological
pathways
may
be
novel
therapeutic
strategy
PE.
Stimulation
natural
disaccharide
trehalose
its
lacto
analog
lactotrehalose
hypoxia-exposed
primary
human
trophoblasts
restored
autophagy,
inhibited
accumulation
toxic
protein
aggregates,
ultrastructural
features
autophagosomes
autolysosomes.
Importantly,
onset
PE-like
humanized
mouse
model
by
normalizing
inhibiting
aggregation
These
disaccharides
autophagy-lysosomal
biogenesis
machinery
increasing
nuclear
translocation
master
transcriptional
regulator
TFEB.
RNA-seq
analysis
placentas
mice
indicated
normalization
PE-associated
transcriptome
profile
response
to
lactotrehalose.
In
summary,
our
results
provide
molecular
rationale
patients
identify
as
promising
options
this
complication.
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 9, 2024
Deoxynivalenol
(DON)
poses
a
serious
global
food
safety
risk
due
to
its
high
toxicity
and
contamination
rate.
It
disrupts
the
intestinal
epithelial
barrier,
allowing
exogenous
toxins
enter
circulation
resulting
in
sepsis
systemic
toxicity.
In
this
research,
32
male
Kunming
mice
Porcine
Small
Intestinal
Epithelial
(IPEC-J2)
cells
were
treated
with
DON
at
0–4.8
mg/kg
(7
d)
0–12
μM
(24
h),
respectively.
Histopathological
results
revealed
that
disrupted
causing
apoptosis
tight
junction
(TJ)
injury.
Immunofluorescence
protein
expression
showed
DON-induced
p53-dependent
mitochondrial
pathway
fibrillar
actin
(F-actin)-associated
TJ
injury
RhoA/ROCK
activated
jejunal
tissue
IPEC-J2
cells.
Pretreatment
RhoA
or
ROCK
inhibitors
(Rosin
Y-27632)
maintained
F-actin-associated
Thus,
induces
damage
barrier
through
pathway-mediated
disruption.
Journal of Central Nervous System Disease,
Год журнала:
2024,
Номер
16
Опубликована: Апрель 22, 2024
Epilepsy
is
a
chronic
neurological
disorder
manifested
by
recurring
unprovoked
seizures
resulting
from
an
imbalance
in
the
inhibitory
and
excitatory
neurotransmitters
brain.
The
process
of
epileptogenesis
involves
complex
interplay
between
reduction
gamma-aminobutyric
acid
(GABA)
enhancement
glutamate.
Pro-BDNF/p75
NTR
expression
augmented
both
glial
cells
neurons
following
epileptic
status
epileptics
(SE).
Over-expression
p75
linked
with
pathogenesis
epilepsy,
augmentation
pro-BDNF/p75
implicated
epilepsy.
However,
precise
mechanistic
function
epilepsy
has
not
been
completely
elucidated.
Therefore,
this
review
aimed
to
revise
pathway
Current Issues in Molecular Biology,
Год журнала:
2025,
Номер
47(2), С. 124 - 124
Опубликована: Фев. 14, 2025
Alzheimer's
disease
(AD)
is
a
neurodegenerative
characterized
by
progressive
cognitive
decline
and
loss
of
neuronal
integrity.
Emerging
evidence
suggests
that
RhoA,
Rho-associated
coiled-coil
kinase
(ROCK),
their
downstream
effector
molecule
glycogen
synthase
3β
(GSK3β)
interact
within
complex
signaling
pathway
(RhoA/ROCK/GSK3β)
plays
crucial
role
in
the
pathogenesis
AD.
small
GTPase,
along
with
its
effector,
ROCK,
regulates
various
cellular
processes,
including
actin
cytoskeleton
dynamics,
apoptosis,
synaptic
plasticity.
GSK3β,
serine/threonine
kinase,
key
function
AD
pathology,
regulation
tau
phosphorylation
amyloid-beta
cleavage.
Overactive
GSK3β
has
been
closely
linked
to
hyperphosphorylation,
neurodegeneration,
progression
Thus,
considered
as
promising
therapeutic
target
for
treating
mitigating
impairment.
However,
clinical
trials
have
faced
considerable
challenges
due
complexity
specific
inhibition
GSK3β.
In
this
review,
we
summarize
literature
regarding
relationship
RhoA/ROCK
pathways
pathogenesis.
We
further
discuss
recent
findings
sTREM2-transgelin-2
(TG2)
axis
potential
mediator
provide
our
review
on
novel
targeting
strategy
Biomedicines,
Год журнала:
2025,
Номер
13(3), С. 649 - 649
Опубликована: Март 6, 2025
Background/Objects:
Rho
signaling
plays
a
role
in
calcium-regulated
cytoskeletal
reorganization
and
cell
movement,
processes
linked
to
neuronal
function
cancer
metastasis.
Gastrodia
elata,
traditional
herbal
medicine,
can
regulate
glutamate-induced
calcium
influx
PC12
cells
influence
by
modulating
cytoskeleton
remodeling
via
the
monoaminergic
system
signaling.
This
study
investigates
effects
of
gastrodin,
key
component
on
signaling,
remodeling,
migration
B35
C6
cells.
It
also
explores
gastrodin’s
impact
prefrontal
cortex
Sprague
Dawley
rats.
Methods:
cells,
rats
were
treated
with
ketamine,
or
both.
The
expression
examined
proteins
from
analyzed
using
immunoblotting.
Immunofluorescent
staining
was
applied
detect
phosphorylation
RhoGDI1.
F-actin
stained
phalloidin-488
staining.
Cell
Transwell
wound-healing
assays.
Results:
Gastrodin
reversed
ketamine-induced
regulation
mobility
inhibition,
condensation,
modulation
including
GDP
dissociation
inhibitor
1
(RhoGDI1);
family
protein
(Ras
homolog
member
A
(RhoA);
division
control
42
(CDC42);
Ras-related
C3
botulinum
toxin
substrate
1(Rac1));
rho-associated,
coiled-coil-containing
kinase
(ROCK1);
neural
Wiskott–Aldrich
syndrome
(NWASP);
myosin
light
chain
2
(MLC2);
profilin1
(PFN1);
cofilin-1
(CFL1)
Similar
modulations
observed
Conclusions:
Our
findings
show
that
gastrodin
counteracts
disruptions
dynamics,
regulating
components
like
RhoGDI1,
ROCK1,
MLC2,
PFN1,
CFL1.
suggests
potential
as
comprehensive
regulator
cellular
Cells,
Год журнала:
2022,
Номер
11(19), С. 3093 - 3093
Опубликована: Окт. 1, 2022
In
this
review,
we
shed
light
on
recent
advances
regarding
the
characterization
of
biochemical
pathways
cellular
mechanosensing
and
mechanotransduction
with
particular
attention
to
their
role
in
neurodegenerative
disease
pathogenesis.
While
mechanistic
components
these
are
mostly
uncovered
today,
crosstalk
between
mechanical
forces
soluble
intracellular
signaling
is
still
not
fully
elucidated.
Here,
recapitulate
general
concepts
mechanobiology
mechanisms
that
govern
processes,
examine
stimuli
response,
highlighting
effect
organelles'
homeostasis
dysfunction.
particular,
discuss
current
knowledge
about
translation
mechanosignaling
into
signaling,
focusing
those
diseases
encompass
metabolic
accumulation
mutant
proteins
have
as
primary
characteristics
formation
pathological
aggregates,
such
Alzheimer's
Disease,
Huntington's
Amyotrophic
Lateral
Sclerosis
Parkinson's
Disease.
Overall,
findings
elucidate
how
may
be
crucial
understand
pathogenic
underlying
emphasize
importance
for
identifying
potential
therapeutic
targets.
Neural Regeneration Research,
Год журнала:
2022,
Номер
18(6), С. 1220 - 1220
Опубликована: Окт. 14, 2022
Aging
is
a
physiological
event
dependent
on
multiple
pathways
that
are
linked
to
lifespan
and
processes
leading
cognitive
decline.
This
process
represents
the
major
risk
factor
for
aging-related
diseases
such
as
Alzheimer's
disease,
Parkinson's
ischemic
stroke.
The
incidence
of
all
these
pathologies
increases
exponentially
with
age.
Research
aging
biology
has
currently
focused
elucidating
molecular
mechanisms
development
those
pathologies.
Cognitive
deficit
neurodegeneration,
common
features
pathologies,
related
alteration
activity
levels
neurotrophic
factors,
brain-derived
factor,
nerve
growth
glial
cell-derived
factor.
For
this
reason,
treatments
modulate
neurotrophin
have
acquired
great
deal
interest
in
preventing
neurodegeneration
promoting
neural
regeneration
several
neurological
diseases.
Those
include
both
direct
administration
factors
induced
expression
viral
vectors,
neurotrophins'
binding
biomaterials
or
other
molecules
increase
their
bioavailability
but
also
cell-based
therapies.
Considering
crucial
role
here
we
discuss
involvement
most
brain
recent
therapeutic
approaches
provide
sustained
support.
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Май 4, 2023
Objective
To
investigate
the
mechanism
underlying
effects
of
berberine
(BBR)
in
treatment
Alzheimer’s
disease
(AD).
Methods
3
×
Tg
AD
mice
were
treated
with
BBR
for
months,
then
open
field
test
(OFT),
novel
object
recognition
(NOR)
and
Morris
water
maze
(MWM)
performed
to
assess
behavioral
performance.
Hematoxylin–eosin
(HE)
staining,
Nissl
staining
used
examine
histopathological
changes.
The
pharmacological
molecular
properties
obtained
from
TCMSP
database.
BBR-associated
targets
identified
using
PharmMapper
(PM),
comparative
toxicogenomics
database
(CTD),
DisGeNet
human
gene
(GeneCards).
Core
networks
PPI
network
functional
enrichment
analyses.
AutoDock
software
was
model
interaction
between
potential
targets.
Finally,
RT-qPCR,
western
blotting
validate
expression
core
Results
Behavioral
experiments,
HE
have
shown
that
can
improve
memory
task
performance
neuronal
damage
hippocampus
mice.
117
identified,
43
genes
downstream
analysis
combination
results
protein–protein
(PPI)
analysis.
2,230
biological
processes
(BP)
terms,
67
cell
components
(CC)
243
function
(MF)
terms
118
KEGG
identified.
ALB
,
EGFR
CASP3
five
PI3K-AKT
signaling
pathway
including
AKT1
HSP90AA1
SRC
HRAS
IGF1
selected
by
analysis,
validated
docking
RT-q
PCR
as
further
Akt1
mRNA
levels
significantly
decreased
increased
after
(
p
<
0.05).
Besides,
AKT
ERK
phosphorylation
group,
their
levels.
Conclusion
AD.
may
exert
a
neuroprotective
effect
modulating
pathways.
