International Journal of Molecular Sciences,
Journal Year:
2019,
Volume and Issue:
20(3), P. 726 - 726
Published: Feb. 8, 2019
Despite
extensive
research
on
epileptogenesis,
there
is
still
a
need
to
investigate
new
pathways
and
targeted
therapeutic
approaches
in
this
complex
process.
Inflammation,
oxidative
stress,
neurotoxicity,
neural
cell
death,
gliosis,
blood–brain
barrier
(BBB)
dysfunction
are
the
most
common
causes
of
epileptogenesis.
Moreover,
renin–angiotensin
system
(RAS)
affects
brain’s
physiological
pathological
conditions,
including
epilepsy
its
consequences.
While
variety
available
pharmacotherapeutic
approaches,
information
high
demand
achievement
treatment
goals
greatly
desired.
Therefore,
targeting
RAS
presents
an
interesting
opportunity
better
understand
This
has
been
supported
by
preclinical
studies,
primarily
based
enzyme,
receptor-inhibition,
selective
agonists,
which
characterized
pleiotropic
properties.
Although
some
antiepileptic
drugs
(AEDs)
that
interfere
with
RAS,
main
therapy
pathway
contributes
synergy
AEDs.
However,
RAS-targeted
alone,
or
combination
AEDs,
requires
clinical
studies
contribute
to,
clarify,
evidence
management.
There
also
genetic
association
between
epilepsy,
involvement
pharmacogenetics
so
possibilities
for
development
diagnostic
personalized
treatments
epilepsy.
Inflammopharmacology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 3, 2025
Abstract
The
currently
approved
drugs
for
Alzheimer’s
disease
(AD)
are
only
symptomatic
treatment
in
the
early
stages
of
but
they
could
not
halt
neurodegeneration,
additionally,
safety
profile
recently
developed
immunotherapy
is
a
big
issue.
This
review
aims
to
explain
importance
repurposing
technique
and
strategy
develop
therapy
AD.
We
illustrated
biological
alterations
pathophysiology
AD
including
amyloid
pathology,
Tau
oxidative
stress,
mitochondrial
dysfunction,
neuroinflammation,
glutamate-mediated
excitotoxicity,
insulin
signaling
impairment,
wingless-related
integration
site/
β
-catenin
signaling,
autophagy.
Additionally,
we
demonstrated
different
repurposed
experimental
models
anti-inflammatory,
anti-hypertensive,
anti-diabetic,
antiepileptic,
antidepressant
anticancer
drugs.
Further,
showed
pipeline
FDA
have
promising
therapeutic
activity
against
AD,
confirming
value
elucidate
curative
Graphical
abstract
Biomedicine & Pharmacotherapy,
Journal Year:
2021,
Volume and Issue:
136, P. 111193 - 111193
Published: Jan. 8, 2021
The
recent
emergence
of
coronavirus
disease-2019
(COVID-19)
as
a
pandemic
affecting
millions
individuals
has
raised
great
concern
throughout
the
world,
and
severe
acute
respiratory
syndrome
coronavirus-2
(SARS-CoV-2)
was
identified
causative
agent
for
COVID-19.
multifunctional
protein
angiotensin
converting
enzyme
2
(ACE2)
is
accepted
its
primary
target
entry
into
host
cells.
In
enzymatic
function,
ACE2,
like
homologue
ACE,
regulates
renin-angiotensin
system
(RAS)
critical
cardiovascular
renal
homeostasis
in
mammals.
Unlike
however,
ACE2
drives
an
alternative
RAS
pathway
by
degrading
Ang-II
thus
operates
to
balance
context
hypertension,
heart
failure,
well
complications
diabetes.
Outside
RAS,
hydrolyzes
key
peptides,
such
amyloid-β,
apelin,
[des-Arg9]-bradykinin.
addition
functions,
found
regulate
intestinal
amino
acid
gut
microbiome.
Although
non-enzymatic
function
receptor
SARS-CoV-2
been
established,
contribution
functions
pathogenesis
COVID-19-related
lung
injury
matter
debate.
A
complete
understanding
this
central
may
begin
explain
various
symptoms
pathologies
seen
infected
individuals,
aid
development
novel
treatments
Aging Cell,
Journal Year:
2021,
Volume and Issue:
20(10)
Published: Sept. 16, 2021
Brain
renin-angiotensin
(Ang)
system
(RAS)
is
implicated
in
neuroinflammation,
a
major
characteristic
of
aging
process.
Angiotensin
II,
produced
by
angiotensin-converting
enzyme
(ACE),
activates
immune
via
angiotensin
type
1
receptor
(AT1),
whereas
Ang(1-7),
generated
ACE2,
binds
with
Mas
(MasR)
to
restrain
excessive
inflammatory
response.
Therefore,
the
present
study
aims
explore
relationship
between
RAS
and
neuroinflammation.
We
found
that
repeated
lipopolysaccharide
(LPS)
treatment
shifted
balance
ACE/Ang
II/AT1
ACE2/Ang(1-7)/MasR
axis
deleterious
side
either
MasR
agonist,
AVE0991
(AVE)
or
ACE2
activator,
diminazene
aceturate,
exhibited
strong
neuroprotective
actions.
Mechanically,
activation
triggered
Forkhead
box
class
O1
(FOXO1)-autophagy
pathway
induced
superoxide
dismutase
(SOD)
catalase
(CAT),
FOXO1-targeted
antioxidant
enzymes.
Meanwhile,
knockdown
FOXO1
BV2
cells,
using
selective
inhibitor,
AS1842856,
animals,
suppressed
translocation
compromised
autophagic
process
activation.
further
used
chloroquine
(CQ)
block
autophagy
showed
suppressing
abrogated
anti-inflammatory
action
AVE.
Likewise,
Ang(1-7)
also
signaling
flux
following
LPS
cells.
Cotreatment
AS1842856
CQ
all
led
inhibition
thereby
abolished
Ang(1-7)-induced
remission
on
NLRP3
inflammasome
caused
exposure,
shifting
microglial
polarization
from
M1
M2
phenotype.
Collectively,
these
results
firstly
illustrated
mechanism
strongly
indicating
involvement
FOXO1-mediated
neuroimmune-modulating
effects
Neurochemical Research,
Journal Year:
2022,
Volume and Issue:
47(8), P. 2345 - 2356
Published: May 20, 2022
Oxytocin
is
a
neuropeptide
hormone
that
plays
an
important
role
in
social
bonding
and
behavior.
Recent
studies
indicate
oxytocin
could
be
involved
the
regulation
of
neurological
disorders.
However,
its
modulating
cognition
Alzheimer's
disease
(AD)
has
never
been
explored.
Hence,
present
study
aims
to
investigate
potential
chronic
intranasal
halting
memory
impairment
&
AD
pathology
aluminum
chloride-induced
female
rats.
Morris
water
maze
was
used
assess
cognitive
dysfunction
two-time
points
throughout
treatment
period.
In
addition,
neuroprotective
effects
were
examined
by
assessing
hippocampal
acetylcholinesterase
activity,
β-amyloid
1-42
protein,
Tau
levels.
ERK1/2,
GSK3β,
caspase-3
levels
assessed
as
chief
neurobiochemical
mediators
AD.
Hippocampi
histopathological
changes
also
evaluated.
These
findings
compared
standard
drug
galantamine
alone
combined
with
oxytocin.
Results
showed
restored
functions
improved
animals'
behavior
test.
This
accompanied
significant
decline
proteins
Hippocampal
ERK1/2
GSK3β
reduced,
exceeding
effects,
thus
attenuating
pathological
hallmarks
formation.
Determination
revealed
low
cytoplasmic
positivity,
indicating
ceasing
neuronal
death.
Histopathological
examination
confirmed
these
findings,
showing
cells
structure.
Combined
even
better
biochemical
profiles.
It
can
concluded
possesses
promising
mediated
via
restoring
suppressing
β-amyloid,
accumulation,
Abstract
Depression
is
a
mood
disorder
characterized
by
abnormal
thoughts.
The
pathophysiology
of
depression
related
to
the
deficiency
serotonin
(5HT),
which
derived
from
tryptophan
(Trp).
Mitochondrial
dysfunction,
oxidative
stress,
and
neuroinflammation
are
involved
in
pathogenesis
depression.
Notably,
renin–angiotensin
system
(RAS)
depression,
different
findings
revealed
that
angiotensin‐converting
enzyme
inhibitors
(ACEIs)
angiotensin
receptor
blockers
(ARBs)
may
be
effective
However,
underlying
mechanism
for
role
dysregulated
brain
RAS‐induced
remains
speculative.
Therefore,
this
review
aimed
revise
conceivable
ACEIs
ARBs
how
these
agents
ameliorate
Dysregulation
RAS
triggers
development
progression
through
reduction
5HT
expression
brain‐derived
neurotrophic
factor
(BDNF)
induction
mitochondrial
neuroinflammation.
inhibition
central
classical
ARBS
activation
non‐classical
prevent
regulating
5HT,
BDNF,
Journal of Cellular and Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
28(12)
Published: June 1, 2024
Abstract
Parkinson
disease
(PD)
is
one
of
the
most
common
neurodegenerative
diseases
brain.
Of
note,
brain
renin‐angiotensin
system
(RAS)
intricate
in
PD
neuropathology
through
modulation
oxidative
stress,
mitochondrial
dysfunction
and
neuroinflammation.
Therefore,
RAS
by
angiotensin
receptor
blockers
(ARBs)
angiotensin‐converting
enzyme
inhibitors
(ACEIs)
may
be
effective
reducing
risk
neuropathology.
It
has
been
shown
that
all
components
including
peptides
enzymes
are
present
different
areas.
Brain
plays
a
critical
role
regulation
memory
cognitive
function,
controlling
central
blood
pressure.
However,
exaggerated
implicated
pathogenesis
PD.
Two
well‐known
pathways
recognized
including;
classical
pathway
which
mainly
mediated
AngII/AT1R
detrimental
effects.
Conversely,
non‐classical
mostly
ACE2/Ang1‐7/MASR
AngII/AT2R
beneficial
effects
against
Exaggerated
affects
viability
dopaminergic
neurons.
fundamental
mechanism
was
not
fully
elucidated.
Consequently,
purpose
this
review
to
disclose
mechanistic
In
addition,
we
try
revise
how
ACEIs
ARBs
can
developed
for
therapeutics
Journal of Clinical Medicine,
Journal Year:
2018,
Volume and Issue:
7(10), P. 329 - 329
Published: Oct. 5, 2018
Recent
studies
have
indicated
that
several
anti-hypertensive
drugs
may
delay
the
development
and
progression
of
Alzheimer's
disease
(AD).
However,
relationships
among
AD,
hypertension,
oxidative
stress
remain
to
be
elucidated.
Here,
we
aimed
determine
whether
reactive
oxygen
species
(ROS)
reduction
by
resveratrol
in
brain
leads
cognitive
impairment
rats
with
angiotensin
II
(Ang-II)-induced
early
AD.
Male
Wistar
Kyoto
(WKY)
Ang-II-induced
AD
were
treated
losartan
or
for
two
weeks.
Our
results
show
decreased
blood
pressure,
increased
hippocampal
brain-derived
neurotrophic
factor
(BDNF)
level,
nucleus
tractus
solitarius
(NTS)
ROS
production
Ang-II
groups
(10
mg/kg),
mg/kg/day)
treatment.
Furthermore,
inhibition
TauT231
phosphorylation
activated
AktS473
phosphorylation,
significantly
abolished
Aβ
precursors,
active
caspase
3,
glycogen
synthase
kinase
3β
(GSK-3β)Y216
expressions.
Consistently,
showed
similar
effects
compared
losartan.
Both
restored
hippocampal-dependent
contextual
memory
NADPH
oxidase
2
(NOX2)
deletion
superoxide
dismutase
(SOD2)
elevation.
suggest
both
exert
neuroprotective
against
damage
stage
rat
model.
These
novel
findings
indicate
represent
a
pharmacological
option
patients
hypertension
at
risk
during
old
age.