Biomedicines,
Год журнала:
2024,
Номер
12(12), С. 2797 - 2797
Опубликована: Дек. 10, 2024
Background:
SGLT-2
inhibitors
(SGLT-2i)
and
GLP-1
receptor
agonists
(GLP-1RA)
have
demonstrated
nephro-
cardioprotective
effects,
but
their
neuroprotective
properties,
especially
concerning
stroke
severity,
mechanisms
are
not
unambiguous.
We
aimed
to
study
the
influence
of
SGLT-2i
with
different
selectivity
GLP-1RA
on
brain
damage
volume
neurological
status
in
non-diabetic
diabetic
rats
investigate
underlying
mechanisms.
Methods:
Non-diabetic
Wistar
were
divided
into
five
groups
(n
=
10
each)
received
empagliflozin,
canagliflozin,
or
dulaglutide
as
drugs
metformin
comparison
drug.
Control
animals
administered
0.9%
NaCl
for
7
days
before
stroke.
At
48
h
after
stroke,
we
assessed
deficit,
neuronal
astroglial
markers,
volume.
also
modeled
type
2
DM
using
high-fat
diet+nicotinamide/streptozotocin
method
established
similar
treatment
groups.
After
8
weeks,
subjected
further
neuroglial
necrosis
measurement.
Results:
In
rats,
all
showed
an
infarct-limiting
effect;
more
effective
than
metformin.
DULA
improved
compared
MET
treatment.
All
decreased
neurofilament
light
chains
(NLCs)
level
none
them
glial
marker
S100BB.
DM,
similarly,
had
effects.
Neurological
deficit
was
most
pronounced
untreated
reduced
by
drugs.
NLC
level;
None
affected
neuron-specific
enolase.
Conclusions:
experimental
might
be
conditions
it
influences
both
status.
decrease
damage,
while
highly
selective
EMPA,
low-selective
CANA,
impact
neuroglia
conditions.
Frontiers in Medicine,
Год журнала:
2025,
Номер
12
Опубликована: Фев. 4, 2025
Alzheimer’s
disease
(AD)
is
the
most
common
cause
of
dementia
and
represents
75%
all
types.
AD
neuropathology
due
to
progressive
deposition
extracellular
amyloid-beta
(A
β
)
peptide
intracellular
hyperphosphorylated
tau
protein.
The
accumulated
Aβ
forms
amyloid
plaques,
while
protein
neurofibrillary
tangles
(NFTs).
Both
plaques
NFTs
are
hallmarks
neuropathology.
fundamental
mechanism
involved
in
pathogenesis
still
elusive,
although
more
conceivable
theory.
Aβ-induced
neurodegeneration
associated
neuroinflammation,
oxidative
stress,
endoplasmic
reticulum
stress
(ER),
mitochondrial
dysfunction
contribute
development
cognitive
impairment
dementia.
Of
note,
not
only
originated
from
brain
but
also
produced
peripherally
and,
via
blood–brain
barrier
(BBB),
can
accumulate
result
AD.
It
has
been
shown
that
cardiometabolic
conditions
such
as
obesity,
type
2
diabetes
(T2D),
heart
failure
(HF)
regarded
possible
risk
factors
for
other
types
dementia,
vascular
HF-induced
chronic
cerebral
hypoperfusion,
inflammation
induce
progression
Interestingly,
a
systemic
causes
which
turn
affects
peripheral
organs,
including
heart.
through
deranged
BBB
be
transported
into
circulation
heart,
leading
HF.
These
findings
suggest
close
relationship
between
However,
exact
AD-induced
HF
fully
elucidated.
Therefore,
this
review
aims
discuss
link
regarding
potential
role
Diabetes Obesity and Metabolism,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 10, 2025
The
effects
of
sodium-glucose
co-transporter
2
inhibitors
(SGLT-2i)
on
dementia
risk
have
not
been
assessed
in
the
Chinese
population.
We
aimed
to
assess
association
between
use
SGLT-2i
and
incidence
a
mainland
A
target
trial
vs.
dipeptidyl
peptidase
4
(DPP-4i)
was
emulated,
with
cohorts
type
diabetes
mellitus
patients
who
were
new
users
or
DPP-4i
being
assembled
using
Yinzhou
Regional
Health
Care
Database.
Inverse
probability
treatment
weighting
(IPTW)
applied
control
potential
confounding,
Cox
model
used
estimate
hazard
ratio
(HR)
incident
dementia.
final
cohort
included
47
335
SGLT-2i.
In
primary
analysis,
500.2
347.5
per
100
000
person-years
SGLT-2i,
respectively.
associated
reduced
after
adjusting
for
confounding
IPTW,
an
HR
0.74
(95%
CI,
0.60-0.93).
results
generally
consistent
various
subgroup
analyses
sensitivity
analyses.
is
decreased
study
population
China.
Communications Biology,
Год журнала:
2025,
Номер
8(1)
Опубликована: Фев. 19, 2025
Although
diabetes
mellitus
is
strongly
associated
with
dementia,
the
mechanism
underlying
diabetes-induced
cognitive
dysfunction
has
not
been
clarified.
Here,
we
demonstrate
vital
role
of
repulsive
guidance
molecule
A
(RGMa)
in
regulation
adult
hippocampal
neurogenesis
and
impairment
under
diabetic
conditions.
In
type
2
db/db
mice
streptozotocin-mediated
1
mice,
RGMa
upregulated
granular
cell
layer
dentate
gyrus.
Additionally,
both
neural
stem
cells
(NSCs)
immature
neurons
express
its
receptor,
neogenin.
vitro
experiments
revealed
that
high
glucose-conditioned
inhibited
differentiation
NSCs,
application
an
anti-RGMa
antibody
restored
it.
The
treatment
ameliorated
decline
neurogenesis.
These
findings
suggest
negatively
regulates
involved
mellitus-induced
decline.
Repulsive
Guidance
Molecule
plays
pivotal
roles
disrupting
diabetes.
Brain Research Bulletin,
Год журнала:
2025,
Номер
224, С. 111296 - 111296
Опубликована: Март 10, 2025
Alzheimer's
disease
(AD)
is
the
chief
cause
of
dementia
and
related
mortality
worldwide
due
to
progressive
accumulation
amyloid
peptide
(Aβ)
hyperphosphorylated
tau
protein.
These
neuropathological
changes
lead
cognitive
impairment
memory
dysfunction.
Notably,
most
Food
drug
Administration
(FDA)
approved
anti-AD
medications
such
as
tacrine
donepezil
are
engaged
with
symptomatic
relief
but
do
not
reverse
underlying
AD
neuropathology.
Therefore,
searching
for
new
advisable.
It
has
been
shown
that
inflammatory
signaling
pathways
mitogen-activated
protein
kinases
(MAPK)
intricate
Aβ
neuropathology
in
AD.
In
addition,
inhibition
brain
MAPK
plays
a
critical
role
mitigating
dysfunction
early-onset
Though,
fundamental
mechanisms
beneficial
effects
inhibitors
were
fully
explained.
this
review
aims
discuss
potential
molecular
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 11, 2025
Glucagon-like
peptide-1
(GLP-1)
receptor
is
widely
distributed
in
the
digestive
system,
cardiovascular
adipose
tissue
and
central
nervous
system.
Numerous
GLP-1
receptor-targeting
drugs
have
been
investigated
clinical
studies
for
various
indications,
including
type
2
diabetes
obesity
(accounts
70%
of
total
studies),
non-alcoholic
steatohepatitis,
Alzheimer's
disease,
Parkinson's
disease.
This
review
presented
fundamental
information
regarding
two
categories
agonists
(GLP-1RAs):
peptide-based
small
molecule
compounds,
elaborated
their
potential
neuroprotective
effects
by
inhibiting
neuroinflammation,
reducing
neuronal
apoptosis,
ultimately
improving
cognitive
function
neurodegenerative
diseases.
As
a
new
hypoglycemic
drug,
GLP-1RA
has
unique
role
concurrent
risk
stroke
T2D
patients.
Given
infiltration
peripheral
immune
cells
into
brain
tissue,
particularly
areas
surrounding
infarct
lesion,
we
further
regulatory
mechanisms.
could
not
only
facilitate
M2
polarization
microglia
through
both
direct
indirect
pathways,
but
also
modulate
quantity
T
cell
subtypes,
CD4,
CD8,
cells,
resulting
inhibition
inflammatory
responses
promotion
regeneration
interleukin-10
secretion.
Therefore,
believe
that
"Tregs-microglia-neuron/neural
precursor
cells"
axis
instrumental
mediating
suppression
neuroprotection
context
ischemic
stroke.
benefits
rapid
diffusion,
favorable
blood-brain
barrier
permeability
versatile
administration
routes,
these
compounds
will
be
one
important
candidates
GLP-1RA.
We
look
forward
to
evidence
intervention
or
complicated
Diabetes Obesity and Metabolism,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 10, 2025
Abstract
Aims
Type
2
diabetes
mellitus
(T2DM)
significantly
increases
the
risk
of
dementia,
including
Alzheimer's
disease
(AD),
vascular
dementia
(VaD)
and
mixed
dementia.
Although
sodium‐glucose
cotransporter‐2
inhibitors
(SGLT2i)
have
shown
potential
neuroprotective
effects,
previous
studies
were
limited
by
small
sample
sizes,
single‐country
datasets
a
lack
detailed
analyses
subtypes.
Materials
Methods
This
retrospective
cohort
study
utilized
TriNetX
database,
comprising
de‐identified
electronic
health
records
from
over
100
million
patients
across
98
healthcare
organizations
worldwide.
Adults
with
T2DM
initiating
treatment
either
SGLT2i
or
dipeptidyl
peptidase‐4
(DPP4i)
between
November
20,
2004,
2024,
included.
Propensity
score
matching
(PSM)
at
1:1
ratio
ensured
balanced
baseline
characteristics.
Primary
outcomes
included
overall
specific
subtypes
(VaD,
AD,
other
dementias),
while
secondary
all‐cause
mortality.
Results
After
propensity
matching,
278
689
per
group
analysed.
use
was
associated
lower
incidence
(2.9%
vs.
6.7%;
adjusted
hazard
[AHR]
0.77,
95%
confidence
interval
[CI],
0.75–0.79)
(AHR
0.80),
0.82)
dementias
0.68).
These
associations
remained
consistent
age,
sex,
glycaemic
control
concurrent
medication
in
subgroup
analyses.
also
linked
to
mortality
(4.1%
11.2%;
AHR
0.66,
CI,
0.65–0.68).
Findings
robust
sensitivity
analyses,
supporting
effects
SGLT2i.
Conclusions
large‐scale
observational
suggests
that
is
risks
multiple
T2DM.
