Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Jan. 26, 2024
The
brain-gut
axis
plays
a
vital
role
in
connecting
the
cognitive
and
emotional
centers
of
brain
with
intricate
workings
intestines.
An
imbalance
microbiota-mediated
extends
far
beyond
conditions
like
Irritable
Bowel
Syndrome
(IBS)
obesity,
playing
critical
development
progression
various
neurological
disorders,
including
epilepsy,
depression,
Alzheimer’s
disease
(AD),
Parkinson’s
(PD).
Epilepsy,
disorder
characterized
by
unprovoked
seizures,
affects
approximately
50
million
people
worldwide.
Accumulating
evidence
suggests
that
rebuilding
gut
microbiota
through
interventions
such
as
fecal
transplantation,
probiotics,
ketogenic
diets
(KD)
can
benefit
drug-resistant
epilepsy.
disturbances
could
contribute
to
toxic
side
effects
antiepileptic
drugs
drug
resistance
epilepsy
patients.
These
findings
imply
potential
impact
on
suggest
targeting
microbiota,
KD,
hold
promise
for
managing
treating
However,
full
extent
importance
treatment
is
not
yet
fully
understood,
many
aspects
this
field
remain
unclear.
Therefore,
article
aims
provide
an
overview
clinical
animal
supporting
regulatory
pathways
within
may
be
influenced
Furthermore,
we
will
discuss
recent
advancements
treatment,
antiseizure
drugs,
all
from
perspective
microbiota.
Neurobiology of Disease,
Journal Year:
2023,
Volume and Issue:
187, P. 106314 - 106314
Published: Oct. 1, 2023
Poly
(ADP-ribose)
polymerase-1
(PARP-1)
is
the
most
extensively
studied
member
of
PARP
superfamily,
with
its
primary
function
being
facilitation
DNA
damage
repair
processes.
Parthanatos
a
type
regulated
cell
death
cascade
initiated
by
PARP-1
hyperactivation,
which
involves
multiple
subroutines,
including
accumulation
ADP-ribose
polymers
(PAR),
binding
PAR
and
apoptosis-inducing
factor
(AIF),
release
AIF
from
mitochondria,
translocation
AIF/macrophage
migration
inhibitory
(MIF)
complex,
massive
MIF-mediated
fragmentation.
Over
past
few
decades,
role
in
central
nervous
system
health
disease
has
received
increasing
attention.
In
this
review,
we
discuss
biological
functions
neural
proliferation
differentiation,
memory
formation,
brain
ageing,
epigenetic
regulation.
We
then
elaborate
on
involvement
PARP-1-dependant
parthanatos
various
neuropathological
processes,
such
as
oxidative
stress,
neuroinflammation,
mitochondrial
dysfunction,
excitotoxicity,
autophagy
damage,
endoplasmic
reticulum
(ER)
stress.
Additional
highlight
contains
PARP-1's
implications
initiation,
progression,
therapeutic
opportunities
for
different
neurological
illnesses,
neurodegenerative
diseases,
stroke,
autism
spectrum
disorder
(ASD),
sclerosis
(MS),
epilepsy,
neuropathic
pain
(NP).
Finally,
emerging
insights
into
repurposing
inhibitors
management
diseases
are
provided.
This
review
aims
to
summarize
exciting
advancements
critical
disorders,
may
open
new
avenues
options
targeting
or
parthanatos.
Brain and Behavior,
Journal Year:
2023,
Volume and Issue:
13(6)
Published: May 23, 2023
Abstract
Introduction
Epilepsy
is
one
of
the
most
common
and
serious
brain
syndromes
has
adverse
consequences
on
a
patient's
neurobiological,
cognitive,
psychological,
social
wellbeing,
thereby
threatening
their
quality
life.
Some
patients
with
epilepsy
experience
poor
treatment
effects
due
to
unclear
pathophysiological
mechanisms
syndrome.
Dysregulation
mammalian
target
rapamycin
(mTOR)
pathway
thought
play
an
important
role
in
onset
progression
some
epilepsies.
Methods
This
review
summarizes
mTOR
signaling
pathogenesis
prospects
for
use
inhibitors.
Results
The
functions
as
vital
mediator
development
through
diverse
mechanisms,
indicating
that
it
great
potential
effective
therapy.
excessive
activation
leads
structural
changes
neurons,
inhibits
autophagy,
exacerbates
neuron
damage,
affects
mossy
fiber
sprouting,
enhances
neuronal
excitability,
increases
neuroinflammation,
closely
associated
tau
upregulation
epilepsy.
A
growing
number
studies
have
demonstrated
inhibitors
exhibit
significant
antiepileptic
both
clinical
applications
animal
models.
Specifically,
rapamycin,
specific
inhibitor
TOR,
reduces
intensity
frequency
seizures.
Clinical
tuberous
sclerosis
complex
shown
function
reducing
seizures
improving
this
disease.
Everolimus,
chemically
modified
derivative
been
approved
added
other
medicines.
Further
explorations
are
needed
evaluate
therapeutic
efficacy
application
value
Conclusions
Targeting
provides
promising
prospect
Cell Death Discovery,
Journal Year:
2023,
Volume and Issue:
9(1)
Published: July 12, 2023
Abstract
Pulmonary
hypertension
(PH)
is
a
clinical
and
pathophysiological
syndrome
caused
by
changes
in
pulmonary
vascular
structure
or
function
that
results
increased
resistance
arterial
pressure,
it
characterized
endothelial
dysfunction,
artery
media
thickening,
remodeling,
right
ventricular
hypertrophy,
all
of
which
are
driven
an
imbalance
between
the
growth
death
cells.
Programmed
cell
(PCD),
different
from
necrosis,
active
cellular
mechanism
activated
response
to
both
internal
external
factors
precisely
regulated
More
than
dozen
PCD
modes
have
been
identified,
among
apoptosis,
autophagy,
pyroptosis,
ferroptosis,
necroptosis,
cuproptosis
proven
be
involved
pathophysiology
PH
varying
degrees.
This
article
provides
summary
regulatory
patterns
their
potential
effects
on
PH.
Additionally,
describes
current
understanding
this
complex
interconnected
process
analyzes
therapeutic
targeting
specific
as
molecular
targets.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Aug. 5, 2024
Sepsis-induced
acute
lung
injury
(ALI)
is
a
major
cause
of
death
among
patients
with
sepsis
in
intensive
care
units.
By
analyzing
model
sepsis-induced
ALI
using
lipopolysaccharide
(LPS)
and
cecal
ligation
puncture
(CLP),
treatment
methods
strategies
to
protect
against
were
discussed,
which
could
provide
an
experimental
basis
for
the
clinical
ALI.
Recent
studies
have
found
that
imbalance
autophagy,
ferroptosis,
pyroptosis
key
mechanism
triggers
ALI,
regulating
these
mechanisms
can
improve
injuries
caused
by
LPS
or
CLP.
This
article
summarized
reviewed
regulatory
networks
their
important
roles
process
LPS/CLP-induced
sepsis,
discusses
possible
targeted
drugs
above
effects,
describes
dilemma
prospects,
provides
new
perspectives
future
Frontiers in Endocrinology,
Journal Year:
2023,
Volume and Issue:
14
Published: March 3, 2023
Diabetic
kidney
disease
(DKD)
is
the
main
cause
of
end-stage
renal
worldwide,
and
there
a
lack
effective
treatment
strategies.
Autophagy
highly
conserved
lysosomal
degradation
process
that
maintains
homeostasis
energy
balance
by
removing
protein
aggregates
damaged
organelles.
Increasing
evidence
suggests
dysregulated
autophagy
may
contribute
to
glomerular
tubulointerstitial
lesions
in
under
diabetic
conditions.
Emerging
studies
have
shown
Chinese
herbal
medicine
its
active
compounds
ameliorate
injury
regulating
autophagy.
In
this
review,
we
summarize
dysregulation
or
insufficiency
cells,
including
podocytes,
mesangial
proximal
tubular
epithelial
key
mechanism
for
development
DKD,
focus
on
protective
effects
compounds.
Moreover,
systematically
reviewed
DKD
regulated
herb
compound
preparations,
single
compounds,
so
as
provide
new
drug
candidates
clinical
DKD.
Finally,
also
candidate
targets
Therefore,
further
research
with
regulation
their
great
significance
realization
targeted
therapies
Frontiers in Cell and Developmental Biology,
Journal Year:
2024,
Volume and Issue:
12
Published: June 12, 2024
Long
non-coding
RNAs
(lncRNAs)
are
a
sort
of
transcripts
that
more
than
200
nucleotides
in
length.
In
recent
years,
many
studies
have
revealed
the
modulatory
role
lncRNAs
cancer.
Typically,
linked
to
variety
essential
events,
such
as
apoptosis,
cellular
proliferation,
and
invasion
malignant
cells.
Simultaneously,
autophagy,
an
intracellular
degradation
mechanism
eukaryotic
cells,
is
activated
respond
multiple
stressful
circumstances,
for
example,
nutrient
scarcity,
accumulation
abnormal
proteins,
organelle
damage.
Autophagy
plays
both
suppressive
promoting
roles
Increasingly,
unveiled
how
dysregulated
expression
can
disrupt
autophagic
balance,
thereby
contributing
cancer
progression.
Consequently,
exploring
interplay
between
autophagy
holds
promising
implications
clinical
research.
this
manuscript,
we
methodically
compiled
advances
molecular
mechanisms
briefly
summarized
lncRNA-mediated
axis.
Neurobiology of Disease,
Journal Year:
2023,
Volume and Issue:
186, P. 106273 - 106273
Published: Aug. 28, 2023
Epilepsy
is
one
of
the
most
common
neurological
disorders.
Neuroinflammation
involving
activation
microglia
and
astrocytes
constitutes
an
important
mechanism
in
epileptogenesis.
Transient
receptor
potential
melastatin
2
(TRPM2)
a
calcium-permeable,
non-selective
cation
channel
that
plays
pathological
roles
various
inflammation-related
diseases.
Our
previous
study
demonstrated
Trpm2
knockout
exhibits
therapeutic
effects
on
pilocarpine-induced
glial
neuroinflammation.
However,
whether
TRPM2
pathogenic
role
this
process
underlying
molecular
mechanisms
remained
undetermined.
Here,
we
demonstrate
previously
unknown
for
microglial
attenuated
kainic
acid
(KA)-induced
activation,
inflammatory
cytokines
production
hippocampal
paroxysmal
discharges,
whereas
exhibited
no
significant
effects.
Furthermore,
discovered
these
were
mediated
by
upregulated
autophagy
via
adenosine
monophosphate
activated
protein
kinase
(AMPK)/mammalian
target
rapamycin
(mTOR)
pathway
microglia.
Thus,
our
findings
highlight
deleterious
temporal
lobe
epilepsy.
Frontiers in Bioscience-Landmark,
Journal Year:
2023,
Volume and Issue:
28(12), P. 323 - 323
Published: Dec. 1, 2023
Background:
Dexmedetomidine
(DEX)
reportedly
protects
against
ischemia-reperfusion
(I/R)
injury
and
associated
damage
to
the
kidneys,
but
underlying
mechanisms
have
yet
be
established.
Methods:
Unilateral
nephrectomy
was
performed
in
Wistar
rats,
remaining
kidney
clamped
for
1
h
prior
reperfusion
establish
an
experimental
model
system.
These
animals
were
then
randomized
into
Sham,
DEX
+
I/R,
ATI
(Altepamizole,
α2-adrenergic
receptor
inhibitor)
3-MA
(3-methyladenine,
autophagy
I/R
groups.
Serum
renal
function
biomarkers,
acute
(AKI)
histopathological
scores,
serum
inflammatory
factors,
redox
markers
of
autophagic
flux,
autophagosome
numbers
assessed.
Levels
proteins
related
pathway,
including
mTOR
AMPK,
also
analyzed.
Results:
creatinine
urea
nitrogen
levels
group
significantly
elevated
over
those
sham
control
as
AKI
cytokine
concentrations
(IL-6,
IL-1β,
TNF-α),
oxidative
stress
biomarker
malondialdehyde
(MDA).
All
these
parameters
reduced
relative
rats.
rats
exhibited
significant
decreases
flux-related
biomarkers
controls,
while
administration
partially
restored
normal
flux
Acute
suppress
expression
AMPK
increasing
expression,
reversed
effects.
The
beneficial
impact
on
I/R-associated
ablated
by
or
administration.
Conclusions:
analyses
provide
strong
evidence
ability
protect
via
α2-AR/AMPK/mTOR
pathway-mediated
enhancement
activity.