Letters in Drug Design & Discovery,
Год журнала:
2023,
Номер
21(14), С. 3060 - 3067
Опубликована: Окт. 31, 2023
Objective:
Vinpocetine
(Vinp),
a
derivative
of
alkaloid
vincristine
with
anti-inflammatory
and
antioxidant
effects,
has
been
shown
to
have
neuroprotective
effects
in
Parkinson's
disease
(PD).
Its
role
mechanisms,
however,
are
not
fully
understood.
Therefore,
the
aim
this
study
was
investigate
possible
mechanisms
Vinp
on
PD
cells.
Methods:
SH-SY5Y
cells
were
treated
then
rotenone
induce
cellular
model
PD.
The
proliferation
level
apoptosis
rate
after
different
treatments
detected
by
MTT
flow
cytometry
assays,
respectively.
Western
blot
used
determine
relative
protein
expression
α-Synuclein
(α-Syn)
differently
Additionally,
commercial
kits
ELISA
oxidative
stress-related
indicators
(superoxide
dismutase
[SOD],
malondialdehyde
[MDA],
reactive
oxygen
species
[ROS])
inflammatory
factors
(tumor
necrosis
factor
α
[TNF-α],
interleukin-5
[IL-5],
interleukin-1β
[IL-1β])
treatments,
Results:
at
concentrations
(5,
10,
50
µM)
had
no
significant
effect
For
rotenone-induced
cells,
pretreatment
could
significantly
reduce
α-Syn
expression,
increased
cell
viability
decreased
apoptosis,
stress
(downregulation
ROS
MDA
levels
upregulation
SOD
activity)
inflammation
(increased
TNF-α,
IL-5,
IL-1β).
In
contrast,
overexpression
SHSY5Y
induction
partially
reversed
aforementioned
protective
Vinp,
causing
decrease
proliferation,
an
increase
rate,
inflammation,
stress.
Conclusion:
exerted
downregulating
promote
inhibit
JAMA Ophthalmology,
Год журнала:
2024,
Номер
142(2), С. 108 - 108
Опубликована: Янв. 4, 2024
Age-related
macular
degeneration
(AMD)
is
a
serious
and
common
ophthalmologic
disorder
that
hypothesized
to
result,
in
part,
from
inflammatory
reactions
the
macula.
Alzheimer
disease
(AD)
treatment,
acetylcholinesterase
inhibitors
(AChEIs),
have
anti-inflammatory
effects
it
remains
unclear
if
they
modify
risk
of
AMD.
Progress in Retinal and Eye Research,
Год журнала:
2024,
Номер
101, С. 101263 - 101263
Опубликована: Апрель 23, 2024
Retinal
diseases
encompass
various
conditions
associated
with
sight-threatening
immune
responses
and
are
leading
causes
of
blindness
worldwide.
These
include
age-related
macular
degeneration,
diabetic
retinopathy,
glaucoma
uveitis.
Emerging
evidence
underscores
the
vital
role
innate
response
in
retinal
diseases,
beyond
previously
emphasized
T-cell-driven
processes
adaptive
system.
In
particular,
pyroptosis,
a
newly
discovered
programmed
cell
death
process
involving
inflammasome
formation,
has
been
implicated
loss
membrane
integrity
release
inflammatory
cytokines.
Several
disease-relevant
animal
models
have
provided
that
formation
inflammasomes
induction
pyroptosis
cells
contribute
to
inflammation
diseases.
this
review
article,
we
summarize
current
knowledge
about
system
We
also
provide
insights
into
translational
targeting
approaches,
including
novel
drugs
countering
improve
diagnosis
treatment
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(20), С. 15430 - 15430
Опубликована: Окт. 21, 2023
In
the
last
two
decades,
there
has
been
increasing
evidence
supporting
non-neuronal
cells
as
active
contributors
to
neurodegenerative
disorders.
Among
glial
cells,
astrocytes
play
a
pivotal
role
in
driving
amyotrophic
lateral
sclerosis
(ALS)
progression,
leading
scientific
community
focus
on
"astrocytic
signature"
ALS.
Here,
we
summarized
main
pathological
mechanisms
characterizing
astrocyte
contribution
MN
damage
and
ALS
such
neuroinflammation,
mitochondrial
dysfunction,
oxidative
stress,
energy
metabolism
impairment,
miRNAs
extracellular
vesicles
contribution,
autophagy
protein
misfolding,
altered
neurotrophic
factor
release.
Since
glutamate
excitotoxicity
is
one
of
most
relevant
features,
focused
specific
this
aspect,
highlighting
known
or
potential
molecular
by
which
participate
level
and,
conversely,
undergo
toxic
effect
excessive
glutamate.
scenario,
can
behave
"producers"
"targets"
high
levels,
going
through
changes
that
affect
themselves
turn,
neuronal
surrounding
thus
actively
impacting
course.
Moreover,
review
aims
point
out
knowledge
gaps
deserve
further
investigation.
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Янв. 23, 2024
Background
Previous
studies
have
explored
the
associations
between
circulating
inflammatory
cytokines
and
blinding
eye
diseases,
including
glaucoma,
cataract
macular
degeneration.
However,
causality
of
these
remains
controversial.
This
study
employs
a
bidirectional
Mendelian
randomization
(MR)
to
investigate
causal
relationships
41
diseases.
Methods
Summary
data
for
cataract,
degeneration
were
publicly
available.
The
inverse
variance
weighted
(IVW)
method
was
employed
as
main
analysis
method.
Additionally,
various
sensitivity
tests,
MR–Egger
regression,
median,
weight
mode,
Cochran’s
Q
test,
MR
pleiotropy
Residual
Sum
Outlier
leave-one-out
conducted
evaluate
stability
results.
Results
IVW
identified
six
causally
associated
with
risk
diseases:
Monokine
induced
by
interferon-gamma
(MIG)
interleukin-1
receptor
antagonist
(IL-1ra),
IL-6,
IL-10,
platelet
derived
growth
factor
BB
(PDGFbb)
MIG
hepatocyte
(HGF)
it
is
noteworthy
that
none
remained
significant
after
Bonferroni
correction
(
p
<
0.0004).
Reverse
analyses
indicated
may
lead
decrease
in
vascular
endothelial
(VEGF)
levels
(OR:
3.326
×
10
−04
,
95%
CI:
5.198
−07
−
2.129
−01
=
0.0151).
Conclusion
highlights
potential
roles
specific
development
Moreover,
suggests
VEGF
likely
be
involved
downstream.
These
findings
offer
insights
early
prevention
novel
therapeutic
strategies
Aging and Disease,
Год журнала:
2025,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2025
Inflammaging
refers
to
chronic,
low-grade
inflammation
that
becomes
more
common
with
age
and
plays
a
central
role
in
the
pathophysiology
of
various
vascular
diseases.
Key
inflammatory
mediators
involved
inflammaging
contribute
endothelial
dysfunction
accelerate
progression
atherosclerosis.
In
addition,
specific
pathological
mechanisms
inflammasomes
have
emerged
as
critical
drivers
immune
responses
within
vasculature.
A
comprehensive
understanding
these
processes
may
lead
innovative
treatment
strategies
could
significantly
improve
management
age-related
Emerging
therapeutic
approaches,
including
cytokine
inhibitors,
senolytics,
specialized
pro-resolving
mediators,
aim
counteract
restore
health.
This
review
seeks
provide
an
in-depth
exploration
molecular
pathways
underlying
highlight
potential
interventions.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 22, 2024
Several
blinding
diseases
affecting
the
retina
and
optic
nerve
are
exacerbated
by
or
caused
dysregulated
inflammation
oxidative
stress.
These
include
uveitis,
age
related
macular
degeneration,
diabetic
retinopathy
glaucoma.
Consequently,
despite
their
divergent
symptoms,
treatments
that
reduce
stress
suppress
may
be
therapeutic.
The
production
of
inflammatory
cytokines
activities
regulated
a
class
proteins
termed
Suppressors
Cytokine
Signaling
(SOCS).
SOCS1
SOCS3
known
to
dampen
signaling
via
pathways
employing
Janus
kinases
signal
transducer
activator
transcription
(JAK/STAT),
Toll-like
Receptors
(TLR),
nuclear
factor
kappa-light-chain-enhancer
activated
B
cells
(NF-κB),
mitogen
kinase
(MAPK)
NLR
family
pyrin
domain
containing
3
(NLRP3).
We
have
developed
cell-penetrating
peptides
from
inhibitory
region
(denoted
as
R9-SOCS1-KIR
R9-SOCS3-KIR)
tested
them
in
retinal
pigment
epithelium
(RPE)
macrophage
cell
lines.
SOCS-KIR
exhibited
anti-inflammatory,
anti-oxidant
anti-angiogenic
properties.
In
culture,
both
Th1
Th17
were
suppressed
together
with
inhibition
other
markers.
also
observed
decrease
oxidants
simultaneous
rise
neuroprotective
effectors.
addition,
treatment
prevented
loss
gap
junction
ensuing
drop
transepithelial
electrical
resistance
RPE
cells.
When
mouse
models
eye
instillation,
they
showed
protection
against
autoimmune
prophylactic
well
Mice
endotoxin-induced
uveitis
protected
administration
well.
R9-SOCS3-KIR
was
particularly
effective
acting
through
STAT3,
e.g.
IL-6
VEGF-A
mediated
responses
lead
degeneration.
Eye
stimulated
antioxidant
effectors
reduced
clinical
symptoms
model
replicates
injury
occurring
AMD.
Because
these
multiple
pathogenic
stimuli
because
can
delivered
topically
cornea,
attractive
candidates
for
therapeutics
Journal of Clinical Medicine,
Год журнала:
2024,
Номер
13(19), С. 5941 - 5941
Опубликована: Окт. 6, 2024
:
This
study
investigates
whether
there
is
an
increased
propensity
to
systemic
conditions
in
patients
with
both
age-related
macular
degeneration
(AMD)
and
glaucoma
order
provide
greater
insight
into
patients'
overall
health
response
physiologic
stress.
