Biomedicines,
Journal Year:
2022,
Volume and Issue:
10(5), P. 1136 - 1136
Published: May 14, 2022
More
than
1
billion
people
live
in
areas
endemic
for
leishmaniasis,
which
is
a
relevant
threat
public
health
worldwide.
Due
to
the
inadequate
treatments,
there
an
urgent
need
develop
novel
alternative
drugs
and
validate
new
targets
fight
this
disease.
One
appealing
approach
selective
inhibition
of
protein
kinases
(PKs),
enzymes
involved
wide
range
processes
along
life
cycle
Leishmania.
Several
PKs,
including
glycogen
synthase
kinase
3
(GSK-3),
have
been
validated
as
essential
parasite
by
genetic
or
pharmacological
methods.
Recently,
chemical
scaffolds
uncovered
Leishmania
GSK-3
inhibitors
with
antiparasitic
activity.
In
order
find
enzyme,
virtual
screening
our
in-house
library
was
carried
out
on
structure
GSK-3.
The
hits
identified
were
experimentally
assayed
both
leishmanicidal
activity
vitro
enzyme.
best
quinone
scaffold.
Their
optimization
through
medicinal
chemistry
led
set
compounds,
provided
frame
establish
biochemical
structure–activity
relationships,
delivered
molecules
improved
selectivity
index.
Altogether,
study
paves
way
systemic
search
class
further
development
potential
drugs.
Biochemical Pharmacology,
Journal Year:
2023,
Volume and Issue:
210, P. 115496 - 115496
Published: March 11, 2023
Neuroinflammation
is
a
critical
degradative
condition
affecting
neurons
in
the
brain.
Progressive
neurodegenerative
conditions
such
as
Alzheimer's
disease
and
Parkinson's
(PD)
have
been
strongly
linked
to
neuroinflammation.
The
trigger
point
for
inflammatory
cells
body
physiological
immune
system.
response
mediated
by
glial
astrocytes
can
rectify
alterations
occurring
cell
time
being
but
prolonged
activation
leads
pathological
progression.
proteins
mediating
an
response,
per
available
literature,
are
undoubtedly
GSK-3β,
NLRP3,
TNF,
PPARγ,
NF-κB,
along
with
few
other
mediatory
proteins.
NLRP3
inflammasome
undeniably
principal
instigator
of
neuroinflammatory
regulatory
pathways
controlling
its
still
unclear,
besides
less
clarity
interplay
between
different
Recent
reports
suggested
involvement
GSK-3β
regulating
activation,
exact
mechanistic
pathway
remains
vague.
In
current
review,
we
attempt
provide
elaborate
description
crosstalk
markers
neuroinflammation
progression,
linking
it
transcription
factors
posttranslational
modification
recent
clinical
therapeutic
advances
targeting
these
also
discussed
parallel
comprehensive
view
progress
made
PD
management
lacunas
existing
field.
The Egyptian Journal of Neurology Psychiatry and Neurosurgery,
Journal Year:
2023,
Volume and Issue:
59(1)
Published: Nov. 7, 2023
Abstract
Alzheimer’s
disease
(AD)
is
a
form
of
dementia
marked
by
the
accumulation
neuritic
plaques
and
neurofibrillary
tangles
through
action
GSK-3β
with
both
significant
epidemiological
clinical
impact.
Current
pharmacological
treatment
approaches
are
focused
on
symptomatic
relief
aims
to
suppress
AD’s
progression
rather
than
modification.
This
issue
has
triggered
further
investigations
about
tau
pathology
as
an
important
component
in
pathophysiology,
one
them
being
Akt
signaling
pathway.
Based
problem
served
AD,
combined
non-existence
conclusive
therapy
for
this
disease;
hence,
study
strives
investigate
potential
therapeutical
benefit
towards
AD.
A
total
82
studies
included,
consisting
national
international
articles
creating
narrative
review
based
PRISMA
checklist.
Variables
searched
study,
include
(AD),
signaling,
serine-9
phosphorylation,
GSK-3β.
Tau
protein
been
mainstay
physiopathology
which
largely
influenced
expression.
shown
inactivate
phosphorylation.
Thus,
modulating
optimizing
pathway
present
encouraging
prospects
development
innovative
efficacious
therapeutic
strategies
addressing
Several
have
tried
estimate
harm
well
dose–effect
relationship
between
concluding
promising
beneficial
effect
AD
therapy.
Here,
we
show
effects
theoretical
empirical
standpoints.
Biomedicines,
Journal Year:
2025,
Volume and Issue:
13(1), P. 115 - 115
Published: Jan. 7, 2025
Postoperative
neurocognitive
dysfunction
(PND)
is
a
prevalent
and
debilitating
complication
in
elderly
surgical
patients,
characterized
by
persistent
cognitive
decline
that
negatively
affects
recovery
quality
of
life.
As
the
aging
population
grows,
rising
number
patients
has
made
PND
an
urgent
clinical
challenge.
Despite
increasing
research
efforts,
pathophysiological
mechanisms
underlying
remain
inadequately
characterized,
underscoring
need
for
more
integrated
framework
to
guide
targeted
interventions.
To
better
understand
molecular
therapeutic
targets
PND,
this
narrative
review
synthesized
evidence
from
peer-reviewed
studies,
identified
through
comprehensive
searches
PubMed,
Embase,
Cochrane
Library,
Web
Science.
Key
findings
highlight
neuroinflammation,
oxidative
stress,
mitochondrial
dysfunction,
neurotransmitter
imbalances,
microvascular
changes,
white
matter
lesions
as
central
pathophysiology,
with
particular
parallels
encephalocele-
sepsis-associated
impairments.
Among
these,
mediated
pathways
such
NLRP3
inflammasome
blood-brain
barrier
disruption,
emerges
pivotal
driver,
triggering
cascades
exacerbate
neuronal
injury.
Oxidative
stress
synergistically
amplify
these
effects,
while
imbalances
alterations,
including
lesions,
contribute
synaptic
decline.
Anesthetic
agents
modulate
interconnected
pathways,
exhibiting
both
protective
detrimental
effects.
Propofol
dexmedetomidine
demonstrate
neuroprotective
properties
suppressing
neuroinflammation
microglial
activation,
whereas
inhalational
anesthetics
like
sevoflurane
intensify
inflammatory
responses.
Ketamine,
its
anti-inflammatory
potential,
offers
promise
but
requires
further
evaluation
determine
long-term
safety
efficacy.
By
bridging
insights
practice,
highlights
critical
role
personalized
anesthetic
strategies
mitigating
improving
patients.
It
aims
inform
future
decision-making
address
multifaceted
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(21), P. 11638 - 11638
Published: Oct. 30, 2024
Neuroinflammation,
characterised
by
the
activation
of
immune
cells
in
central
nervous
system
(CNS),
plays
a
dual
role
both
protecting
against
and
contributing
to
progression
neurodegenerative
diseases,
such
as
Alzheimer's
disease
(AD)
multiple
sclerosis
(MS).
This
review
explores
phosphoinositide
3-kinase
(PI3K),
key
enzyme
involved
cellular
survival,
proliferation,
inflammatory
responses,
within
context
neuroinflammation.
Two
PI3K
isoforms
interest,
PI3Kγ
PI3Kδ,
are
specific
regulation
CNS
cells,
microglia,
astrocytes,
neurons,
oligodendrocytes,
influencing
pathways,
Akt,
mTOR,
NF-κB,
that
control
cytokine
production,
cell
activation,
neuroprotection.
The
dysregulation
signalling
is
implicated
chronic
neuroinflammation,
exacerbation
diseases.
Preclinical
studies
show
promise
targeting
neuronal
disorders
using
inhibitors,
AS605240
(PI3Kγ)
idelalisib
(PI3Kδ),
which
have
reduced
inflammation,
microglial
death
vivo
models
AD.
However,
clinical
translation
these
inhibitors
faces
challenges,
including
blood-brain
barrier
(BBB)
permeability,
isoform
specificity,
long-term
safety
concerns.
highlights
therapeutic
potential
modulation
neuroinflammatory
identifying
gaps
current
research,
particularly
need
for
brain-penetrating
isoform-specific
inhibitors.
These
findings
underscore
importance
future
research
develop
targeted
therapies
can
effectively
modulate
activity
provide
neuroprotection
disorders.
Biomedicines,
Journal Year:
2025,
Volume and Issue:
13(2), P. 527 - 527
Published: Feb. 19, 2025
Background/Objectives:
Bone
regeneration
using
nanomaterial-based
approaches
shows
promise
for
treating
critical
bone
defects.
However,
developing
sustainable
and
cost-effective
therapeutic
materials
remains
challenging.
This
study
investigates
the
osteogenic
potential
of
clove-derived
carbon
dots
(C-CDs)
applications.
Methods:
C-CDs
were
synthesized
a
green
hydrothermal
method.
The
was
evaluated
in
human
marrow-derived
mesenchymal
stem
cells
(hBM-MSCs)
validated
ectopic
formation
calvarial
defect
models.
Results:
demonstrated
uniform
morphology
(~10
nm)
with
efficient
cellular
uptake.
In
vitro
studies
showed
successful
differentiation
through
upregulation
RUNX2,
ALP,
COL1A1,
BMP-2
mediated
by
Wnt/β-catenin/GSK3β
BMP
signaling
pathways.
vivo
models
have
also
that
are
effective
promoting
regeneration.
Conclusions:
These
findings
establish
as
promising
candidates
therapy,
offering
alternative
to
current
treatments.
While
optimization
is
needed,
their
properties
warrant
further
development
regenerative
medicine
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(15), P. 8263 - 8263
Published: July 29, 2024
Nowadays,
GSK3
is
accepted
as
an
enzyme
strongly
involved
in
the
regulation
of
inflammation
by
balancing
pro-
and
anti-inflammatory
responses
cells
organisms,
thus
influencing
initiation,
progression,
resolution
inflammatory
processes
at
multiple
levels.
Disturbances
within
its
broad
functional
scope,
either
intrinsically
or
extrinsically
induced,
harbor
risk
profound
disruptions
to
regular
course
immune
response,
including
formation
severe
inflammation-related
diseases.
Therefore,
this
review
aims
summarizing
contextualizing
current
knowledge
derived
from
animal
models
further
shape
our
understanding
GSK3α
β
their
roles
process
occurrence
tissue/organ
damage.
Following
a
short
recapitulation
structure,
function,
GSK3,
we
will
focus
on
lessons
learned
GSK3α/β
knock-out
knock-in/overexpression
models,
both
conventional
conditional,
well
variety
(predominantly
rodent)
disease
reflecting
defined
pathologic
conditions
with
significant
proportion
tissue
injury.
In
summary,
literature
suggests
that
acts
crucial
switch
driving
pro-inflammatory
destructive
contributes
significantly
pathogenesis
inflammation-associated
npj Biofilms and Microbiomes,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: Aug. 29, 2024
The
ISS
rodent
habitat
has
provided
crucial
insights
into
the
impact
of
spaceflight
on
mammals,
inducing
symptoms
characteristic
liver
disease,
insulin
resistance,
osteopenia,
and
myopathy.
Although
these
physiological
responses
can
involve
microbiome
Earth,
host-microbiota
interactions
during
are
still
being
elucidated.
We
explore
murine
gut
microbiota
host
gene
expression
in
colon
after
29
56
days
using
multiomics.
Metagenomics
revealed
significant
changes
44
species,
including
relative
reductions
bile
acid
butyrate
metabolising
bacteria
like
Extibacter
muris
Dysosmobacter
welbionis.
Functional
prediction
indicate
over-representation
fatty
metabolism,
extracellular
matrix
interactions,
antibiotic
resistance
genes.
Host
described
corresponding
to
energy
immune
suppression.
These
imply
that
at
host-gut
interface
contribute
pathology
might
critically
influence
human
health
long-duration
feasibility.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(5), P. 1134 - 1134
Published: May 20, 2023
Parkinson’s
disease
(PD)
is
the
fastest-growing
neurodegeneration
disease,
characterized
typically
by
a
progressive
loss
of
dopaminergic
neurons
in
substantia
nigra,
and
there
are
no
effective
therapeutic
agents
to
cure
PD.
Rotenone
(Rot)
common
widely
used
pesticide
which
can
directly
inhibit
mitochondrial
complex
I,
leading
neurons.
Our
previous
studies
proved
that
JWA
gene
(arl6ip5)
may
play
prominent
role
resisting
aging,
oxidative
stress
inflammation,
knockout
astrocytes
increases
susceptibility
mice
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-induced
JWA-activating
compound
4
(JAC4)
small-molecule
activator
gene,
but
its
mechanism
against
PD
have
not
yet
been
clarified.
In
present
study,
we
showed
expression
level
strongly
related
tyrosine
hydroxylase
(TH)
different
growth
periods
mice.
Additionally,
constructed
models
with
Rot
vivo
vitro
observe
neuroprotective
effects
JAC4.
results
demonstrated
JAC4
prophylactic
intervention
improved
motor
dysfunction
neuron
Mechanistically,
reduced
damage
reversing
I
damage,
reducing
nuclear
factor
kappa-B
(NF-κB)
translocation
repressing
nucleotide-binding
domain,
leucine-rich-containing
family
pyrin
domain-containing-3
(NLRP3)
inflammasome
activation.
Overall,
our
provide
proof
could
serve
as
novel
agent
for
prevention.