Journal of Alzheimer s Disease,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 20, 2025
Background
Alzheimer's
disease
(AD)
is
a
chronic
brain
degenerative
that
leads
to
dementia.
Objective
The
aim
of
the
present
study
investigate
neuroprotective
impact
sodium-glucose
cotransporter-2
inhibitors
(SGLT2i)
(empagliflozin
and
dapagliflozin)
on
tau
phosphorylation,
oxidative
stress,
neuroinflammation.
Methods
We
used
MTT
(3-(4,
5-dimethylthiazolyl-2)-2,
5-diphenyltetrazolium
bromide)
assay,
annexin-V-FITC
kit,
DCFH-DA
(dichloro-dihydro-fluorescein
diacetate)
respectively
evaluate
effect
SGLT2i
amyloid-β
(Aβ)
1–42
-induced
neuronal
death,
apoptosis,
stress.
expression
NLRP3-inflammasome,
phospho-Tau181,
glycogen
synthase
kinase-3
beta
(GSK-3β),
cyclin-dependent
kinase
5
(CdK5),
histone
deacetylase
6
(HDAC6),
was
quantified
by
flow
cytometry.
Drug
distribution
in
mice's
brains
assessed
liquid
chromatography-mass
spectrometry
(LC-MS).
Results
Aβ
significantly
reduced
cell
viability
increased
which
reversed
using
gliflozins.
reactive
oxygen
species
generation,
downregulated
diminished
pathology.
Mechanistically,
last
involved
modulation
GSK-3β
CdK5
protein
expression.
However,
tested
treatments
did
not
modify
-stimulating
HDAC6.
Gliflozins
are
substrates
drug
transporters
ATP-binding
cassette
sub-family
B
member
1
and/or
ATP
binding
subfamily
G
2
(ABCB1
ABCG2),
Elacridar
enhances
their
distribution.
Conclusions
empagliflozin
dapagliflozin
exhibited
actions
against
human
neurotoxicity.
Cells,
Journal Year:
2025,
Volume and Issue:
14(7), P. 507 - 507
Published: March 29, 2025
Empagliflozin
(EMPA),
a
sodium-glucose
co-transporter
2
(SGLT2)
inhibitor,
prevents
endothelial
dysfunction,
but
its
effects
on
vascular
tone
in
hypertension
remain
unclear.
This
study
investigated
whether
EMPA
modulates
vasomotor
via
sirtuin
1
(SIRT1)
and
AMP-activated
protein
kinase
(AMPK)
pathways
spontaneously
hypertensive
rats
(SHR)
controls
(Wistar
Kyoto
rats,
WKY).
Functional
(wire
myography,
organ
bath)
biochemical
(Western
blot)
studies
were
conducted
the
third-order
of
superior
mesenteric
arteries
(sMAs)
and/or
aortas.
induced
concentration-dependent
relaxation
preconstricted
sMAs
both
groups.
In
SHR,
enhanced
acetylcholine
(Ach)-induced
aortas
reduced
constriction
by
phenylephrine
(Phe)
U46619
sMAs.
The
SIRT1
inhibitor
(EX527)
abolished
EMPA’s
Ach-mediated
U46619-induced
vasoconstriction,
while
AMPK
inhibition
Phe-induced
vasoconstriction.
SHR
showed
increased
SGLT2
expression
decreased
pAMPK/AMPK
levels
conclusion,
might
exert
vasoprotective
enhancing
endothelium-dependent
reducing
AMPK/SIRT1
pathways.
These
properties
could
improve
health
patients
with
related
conditions.
Further
are
needed
to
explore
new
indications
for
inhibitors.
Cells,
Journal Year:
2024,
Volume and Issue:
13(22), P. 1876 - 1876
Published: Nov. 13, 2024
Glucose
metabolism
is
essential
for
the
maintenance
and
function
of
central
nervous
system.
Although
brain
constitutes
only
2%
body
weight,
it
consumes
approximately
20%
body’s
total
energy,
predominantly
derived
from
glucose.
This
high
energy
demand
underscores
its
reliance
on
glucose
to
fuel
various
functions,
including
neuronal
activity,
synaptic
transmission,
ion
gradients
necessary
nerve
impulse
transmission.
Increasing
evidence
shows
that
many
neurodegenerative
diseases,
Parkinson’s
disease
(PD),
are
associated
with
abnormalities
in
metabolism.
PD
characterized
by
progressive
loss
dopaminergic
neurons
substantia
nigra,
accompanied
accumulation
α-synuclein
protein
aggregates.
These
pathological
features
exacerbated
mitochondrial
dysfunction,
oxidative
stress,
neuroinflammation,
all
which
influenced
disruptions.
Emerging
suggests
targeting
could
offer
therapeutic
benefits
PD.
Several
antidiabetic
drugs
have
shown
promise
animal
models
clinical
trials
mitigating
symptoms
progression
review
explores
current
understanding
association
between
metabolism,
emphasizing
potential
medications
as
a
novel
approach.
By
improving
uptake
utilization,
enhancing
function,
reducing
these
address
key
pathophysiological
mechanisms
PD,
offering
hope
more
effective
management
this
debilitating
disease.
3.9
million
individuals
rely
on
kidney
replacement
therapy
worldwide.
They
experience
height-ened
susceptibility
to
cardiovascular
diseases
and
mortality,
alongside
an
increased
risk
of
in-fections
malignancies,
with
inflammation
being
key
explaining
this
intensified
risk.
This
study
utilized
semi-targeted
metabolomics
explore
novel
metabolic
pathways
related
in-flammation
in
populations.
We
collected
pre
post-session
blood
samples
patients
who
had
already
undergone
one
year
chronic
hemodialysis.
And
used
liquid
chromatography
high
resolution
mass
spectrometry
perform
a
metabolomic
analysis.
Afterwards,
we
employed
both
univariate
(Mann-Whitney
test)
multivariate
(logistic
regression
LASSO
regulari-zation)
identify
metabolites
associated
inflammation.
In
the
analysis,
in-dole-3-acetaldehyde,
2-ketobutyric
acid,
urocanic
acid
showed
statistically
significant
de-creases
median
concentrations
presence
positively
include
allantoin,
taurodeoxycholic
norepinephrine,
pyroglutamic
L-hydroorotic
acid.
Conversely,
showing
negative
associations
benzoic
indole-3-acetaldehyde,
methio-nine,
citrulline,
alphaketoglutarate,
n-acetyl-ornithine
3-4-dihydroxibenzeneacetic
Non
inflamed
exhibit
preserved
autophagy
reduced
mitochondrial
dysfunction.
Under-standing
group
hinges
metabolism
arginine
urea
cycle.
Additionally,
microbiota,
particularly
uricase-producing
bacteria
those
metabolizing
tryptophan,
play
critical
roles.
Journal of Biochemical and Molecular Toxicology,
Journal Year:
2024,
Volume and Issue:
38(12)
Published: Dec. 1, 2024
ABSTRACT
One
of
the
key
challenges
in
medical
research
is
developing
safe
medications
to
treat
neurodegenerative
disorders.
Increased
oxidative
stress,
mitochondrial
dysfunction,
and
neuroinflammation
are
common
features
Alzheimer's
disease
(AD)
Parkinson's
(PD).
Silent
information
regulator
1
(SIRT‐1),
part
sirtuin
family,
plays
a
critical
role
various
physiological
processes
by
binding
histones
nonhistone
proteins.
SIRT‐1
primarily
mitigates
stress
regulates
activity
maintaining
deacetylated
form
peroxisome
proliferator‐activated
receptor‐γ
coactivator‐1α
(PGC‐1α),
ensuring
stable
PGC‐1α
levels.
Research
has
shown
reduced
SIRT‐1/PGC‐1α
expression
AD
PD
models.
Targeting
this
pathway
presents
promising
therapeutic
approach
for
managing
PD,
potentially
leading
disease‐modifying
treatments
improved
outcomes.
This
review
highlights
findings
studies
suggesting
that
promotes
biogenesis,
synaptic
plasticity,
cognitive
function,
as
well
exerts
antioxidant,
anti‐inflammatory,
anti‐apoptotic
effects,
offering
potential
method
treatment.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(17), P. 9364 - 9364
Published: Aug. 29, 2024
Worldwide,
3.9
million
individuals
rely
on
kidney
replacement
therapy.
They
experience
heightened
susceptibility
to
cardiovascular
diseases
and
mortality,
alongside
an
increased
risk
of
infections
malignancies,
with
inflammation
being
key
explaining
this
intensified
risk.
This
study
utilized
semi-targeted
metabolomics
explore
novel
metabolic
pathways
related
in
population.
We
collected
pre-
post-session
blood
samples
patients
who
had
already
undergone
one
year
chronic
hemodialysis
used
liquid
chromatography
high-resolution
mass
spectrometry
perform
a
metabolomic
analysis.
Afterwards,
we
employed
both
univariate
(Mann–Whitney
test)
multivariate
(logistic
regression
LASSO
regularization)
identify
metabolites
associated
inflammation.
In
the
analysis,
indole-3-acetaldehyde,
2-ketobutyric
acid,
urocanic
acid
showed
statistically
significant
decreases
median
concentrations
presence
positively
included
allantoin,
taurodeoxycholic
norepinephrine,
pyroglutamic
L-hydroorotic
acid.
Conversely,
showing
negative
associations
benzoic
methionine,
citrulline,
alphaketoglutarate,
n-acetyl-ornithine,
3-4-dihydroxibenzeneacetic
Non-inflamed
exhibit
preserved
autophagy
reduced
mitochondrial
dysfunction.
Understanding
group
hinges
metabolism
arginine
urea
cycle.
Additionally,
microbiota,
particularly
uricase-producing
bacteria
those
metabolizing
tryptophan,
play
critical
roles.
