The role of the brain renin-angiotensin system in Parkinson´s disease
Translational Neurodegeneration,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: April 15, 2024
Abstract
The
renin-angiotensin
system
(RAS)
was
classically
considered
a
circulating
hormonal
that
regulates
blood
pressure.
However,
different
tissues
and
organs,
including
the
brain,
have
local
paracrine
RAS.
Mutual
regulation
between
dopaminergic
RAS
has
been
observed
in
several
tissues.
Dysregulation
of
these
interactions
leads
to
renal
cardiovascular
diseases,
as
well
progression
neuron
degeneration
major
brain
center
dopamine/angiotensin
interaction
such
nigrostriatal
system.
A
decrease
function
induces
upregulation
angiotensin
type-1
(AT1)
receptor
activity,
leading
recovery
dopamine
levels.
AT1
overactivity
neurons
microglial
cells
upregulates
cellular
NADPH-oxidase-superoxide
axis
Ca
2+
release,
which
mediate
key
events
oxidative
stress,
neuroinflammation,
α-synuclein
aggregation,
involved
Parkinson's
disease
(PD)
pathogenesis.
An
intraneuronal
antioxidative/anti-inflammatory
counteracts
effects
pro-oxidative
overactivity.
Consistent
with
this,
an
imbalance
activity
towards
pro-oxidative/pro-inflammatory
substantia
nigra
striatum
animal
models
high
vulnerability
degeneration.
Interestingly,
autoantibodies
against
angiotensin-converting
enzyme
2
receptors
are
increased
PD
patients
contribute
blood–brain
barrier
(BBB)
dysregulation
pro-inflammatory
upregulation.
Therapeutic
strategies
addressed
modulation
RAS,
by
blockers
(ARBs)
and/or
activation
antioxidative
(AT2,
Mas
receptors),
may
be
neuroprotective
for
individuals
risk
developing
or
prodromal
stages
reduce
disease.
Language: Английский
The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?
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
Language: Английский
Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis
Egyptian Journal of Medical Human Genetics,
Journal Year:
2025,
Volume and Issue:
26(1)
Published: March 4, 2025
Abstract
Background
Huntington's
disease
(HD)
could
cause
progressive
motor
deficits,
psychiatric
symptoms,
and
cognitive
impairment.
With
the
increasing
use
of
pharmacotherapies
theoretically
target
neurotransmitters,
incidence
HD
is
still
not
decreasing.
However,
molecular
pathogenesis
have
been
illuminate.
It
momentous
to
further
examine
HD.
Methods
The
next
generation
sequencing
dataset
GSE105041
was
downloaded
from
Gene
Expression
Omnibus
(GEO)
database.
Using
DESeq2
in
R
bioconductor
package
screen
differentially
expressed
genes
(DEGs)
between
samples
normal
control
samples.
ontology
(GO)
term
REACTOME
pathway
enrichment
were
performed
on
DEGs.
Meanwhile,
using
Integrated
Interactions
Database
(IID)
database
Cytoscape
software
construct
protein–protein
interaction
(PPI)
network
module
analysis,
identify
hub
with
highest
value
node
degree,
betweenness,
stress
closeness
scores.
miRNA-hub
gene
regulatory
TF-hub
constructed
analyzed.
Receiver
operating
characteristic
curves
analysis
for
diagnostic
genes.
Results
We
identified
958
DEGs,
consisting
479
up
regulated
DEGs
down
GO
terms
analyses
by
g:Profiler
online
results
revealed
that
mainly
enriched
multicellular
organismal
process,
developmental
signaling
GPCR
MHC
class
II
antigen
presentation.
Network
Analyzer
plugin
PPI
network,
LRRK2,
MTUS2,
HOXA1,
IL7R,
ERBB3,
EGFR,
TEX101,
WDR76,
NEDD4L
COMT
selected
as
Hsa-mir-1292-5p,
hsa-mir-4521,
ESRRB
SREBF1
are
potential
biomarkers
predicted
be
associated
Conclusion
This
study
investigated
key
pathways
interactions
its
complications,
which
might
help
reveal
correlation
complications.
current
investigation
captured
prediction,
follow-up
biological
experiments
enforced
validation.
Language: Английский
Therapeutic Efficacy of Small Extracellular Vesicles Loaded with ROCK Inhibitor in Parkinson’s Disease
Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
17(3), P. 365 - 365
Published: March 13, 2025
Background/Objectives:
Parkinson’s
disease
(PD)
is
a
rapidly
growing
neurological
disorder
in
the
developed
world,
affecting
millions
over
age
of
60.
The
decline
motor
functions
occurs
due
to
progressive
loss
midbrain
dopaminergic
neurons,
resulting
lowered
dopamine
levels
and
impaired
muscle
function.
Studies
show
defective
mitochondrial
autophagy
(or
“mitophagy”)
links
PD.
Rho-associated
coiled-coil
containing
protein
kinases
(ROCK)
1
ROCK2
are
serine/threonine
kinases,
their
inhibition
can
enhance
neuroprotection
PD
by
promoting
mitophagy.
Methods:
We
examine
effects
ROCK
inhibitor
SR3677,
delivered
via
macrophage-derived
small
extracellular
vesicles
(sEVs)
Parkin
Q311X(A)
mouse
models.
sEVs
with
administered
intranasally,
increased
mitophagy
gene
expression,
reduced
inflammatory
factors,
elevated
brain
tissues.
Results:
expression
decreased,
showing
drug’s
inhibitory
effect.
sEV-SR3677
treatment
was
more
effective
than
drug
alone,
although
sham
EVs
showed
lower
effects.
This
suggests
that
EV-SR3677
not
only
activates
processes
but
also
promotes
degradation
damaged
mitochondria
through
autophagy.
Mitochondrial
functional
assays
oxygen
consumption
ex
vivo
glial
cultures
revealed
significantly
improved
respiration
compared
untreated
or
SR3677-only
treated
cells.
Conclusion:
demonstrated
efficacy
on
function
model,
necessitating
further
studies
explore
design
challenges
mechanisms
as
mitochondria-targeted
therapy
for
Language: Английский
Olfactory mucosal mesenchymal stem cell-derived exosome Lnc A2M-AS1 ameliorates oxidative stress by regulating TP53INP1-mediated mitochondrial autophagy through interacting with IGF2BP1 in Parkinson’s diseases
Cell Biology and Toxicology,
Journal Year:
2025,
Volume and Issue:
41(1)
Published: March 20, 2025
Abstract
Background
Exosome
Lnc
A2M-AS1
from
olfactory
mucosa
mesenchymal
stem
cells
(OM-MSCs)
can
ameliorate
oxidative
stress
by
improving
mitophagy
in
cardiomuscular
cells;
however,
it
remains
unclear
whether
this
effect
exists
the
brain
tissues
of
patients
with
Parkinson’s
disease
(PD).
Methods
OM-MSC–Exosomes
were
isolated
and
verified
based
on
morphology
specific
biomarkers.
The
effects
OM-MSC-Exo
mitochondrial
autophagy,
stress,
lncRNA
detected
MPP
+
-treated
HT22
cells.
OM-MSC-Exos
autophagy
an
MPTP-induced
Parkinson's
(PD)
model
C57BL/6
mice.
interaction
between
IGF2BP1,
A2M-AS1,
TP53INP1
was
assessed
via
RNA
pull-down/RNA
Immunoprecipitation
stability
assays.
lnc
IGF2BP1/TP53INP1-mediated
PD
mouse
models.
Results
Exosomes
found
to
be
rich
A2M-AS1.
proved
able
induced
regulates
enhancing
In
addition,
through
mediated
expression
binding
IGF2BP1.
Furthermore,
treatment
improved
symptoms
ameliorated
Conclusion
Collectively,
OM-MSC-derived
exosomes
targeting
IGF2BP1
induce
stress.
could
potentially
serve
as
promising
candidates
for
new
methods
PD.
Graphical
Language: Английский