FOCUS Endocrinology,
Journal Year:
2025,
Volume and Issue:
6(1), P. 20 - 30
Published: May 16, 2025
The
new
cardio-reno-metabolic
strategy
in
the
monitoring
and
treatment
of
patients
with
type
2
diabetes
mellitus
(T2DM)
obliges
clinician
to
increasingly
prefer
early
combination
therapy,
which
provides
not
only
reliable
safe
glycemic
control,
but
also
protection
against
cardio-renal
complications
T2DM.
drugs
that
meet
these
requirements
are
sodium-glucose
cotransporter
inhibitors
glucagon-like
peptide-1
(GLP-1)
receptor
agonists,
have
shown
a
high
efficacy
safety
profile,
reduced
risk
major
cardiovascular
diseases,
chronic
kidney
disease
mortality.
Moreover,
it
is
currently
known
pleiotropic
effects
limited
protection.
This
article
discusses
latest
data
on
GLP-1
open
up
completely
unexpected
prospects
for
use
drugs,
such
as
heart
failure,
non-alcoholic
fatty
liver
disease,
steatohepatitis
neurodegenerative
diseases.
Frontiers in Aging,
Journal Year:
2025,
Volume and Issue:
6
Published: March 20, 2025
Alzheimer’s
disease
(AD)
is
the
most
common
age-related
neurodegenerative
and
cause
of
dementia.
AD
pathology
primarily
involves
formation
amyloid
β
(Aβ)
plaques
neurofibrillary
tangles
containing
hyperphosphorylated
tau
(p-tau).
While
Aβ
targeted
treatments
have
shown
clinical
promise,
other
aspects
such
as
microgliosis,
astrocytosis,
synaptic
loss,
hypometabolism
may
be
viable
targets
for
treatment.
Among
notable
novel
therapeutic
approaches,
Ras
homolog
(Rho)-associated
kinases
(ROCKs)
are
being
investigated
treatment,
based
on
observations
that
ROCK1/2
levels
elevated
in
AD,
activation
or
inhibition
ROCKs
changes
dendritic/synaptic
structures,
protein
aggregate
accumulation,
inflammation,
gliosis.
This
review
will
highlight
key
findings
effects
ROCK
ptau
pathologies,
well
its
neuroinflammation,
density,
potentially
metabolism
bioenergetics.
Journal of Neurology Neurosurgery & Psychiatry,
Journal Year:
2025,
Volume and Issue:
unknown, P. jnnp - 335593
Published: April 10, 2025
Disease-modifying
treatments
for
major
neurocognitive
disorders,
including
Alzheimer’s
disease,
Parkinson’s
disease
and
other
cognitive
deficits,
are
among
the
main
unmet
needs
in
modern
medicine.
Glucagon-like
peptide-1
receptor
agonists
(GLP-1RAs),
currently
licensed
treatment
of
type
2
diabetes
mellitus
obesity,
offer
a
novel,
multilayered
mechanism
intervention
neurodegeneration
through
intermediate,
aetiology-agnostic
pathways,
likely
involving
metabolic,
inflammatory
several
relevant
neurobiological
processes.
In
vitro
animal
studies
have
revealed
promising
signals
neuroprotection,
with
preliminary
supportive
evidence
emerging
from
recent
pharmacoepidemiological
investigations
clinical
trials.
this
article,
we
comprehensively
review
that
investigate
impact
GLP-1RAs
on
various
aetiologies
impairment
dementia
syndromes.
Focusing
human
studies,
highlight
how
brain
energy
homeostasis,
neurogenesis,
synaptic
functioning,
neuroinflammation
cellular
stress
responses,
pathological
protein
aggregates,
proteostasis,
cerebrovascular
system
blood-brain
barrier
dynamics
may
underlie
GLP-1RA
putative
neuroprotective
effects.
We
then
report
appraise
observational
investigations,
trials
pooled
analyses.
Finally,
discuss
current
challenges
perspectives
ahead
research
implementation
care
people
their
individual
penetrance
potential,
need
response
biomarkers
stage-based
indications,
possible
non-specific
effects
health,
profile
terms
adverse
events
unwanted
effects,
lack
long-term
data
efficacy
safety,
issues
surrounding
cost
availability
treatment.
The Journal of Prevention of Alzheimer s Disease,
Journal Year:
2025,
Volume and Issue:
unknown, P. 100163 - 100163
Published: April 1, 2025
Following
the
recent
approvals
of
anti-amyloid
immunotherapies
as
"first-in-kind"
disease-modifying
agents
for
Alzheimer's
disease
(AD),
there
is
an
emerging
emphasis
in
combination
therapies,
given
complex
and
multifactorial
etiopathogenesis
pathophysiology
disease.
The
EU/US
CTAD
Task
Force
met
Madrid
October
2024,
to
discuss
biological
rationale
methodological
issues
outline
potential
directions
future
research
therapies.
agreed
on
necessity
urgency
advancing
therapies
AD
treatment.
As
January
1,
drug
development
pipeline,
were
21
trials
(13
%
all
trials).
anti-tau
could
become
a
central
focus
field.
Combinations
involving
anti-inflammatory
immune
mechanisms
with
or
other
also
have
promise.
To
facilitate
implementation
collaborations
between
sponsors
public-private
partnerships
are
essential.
Optimizing
likelihood
success
primarily
requires
leveraging
use
biomarkers
clearer
understanding
underpinning
their
interactions,
especially
those
amyloid,
tau,
inflammation,
that
lead
cognitive
decline
progression.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(9), P. 4095 - 4095
Published: April 25, 2025
Clinical
data
as
well
animal
and
cell
studies
indicate
that
certain
antidiabetic
drugs,
including
glucagon-like
peptide
1
receptor
agonists
(GLP-1RAs),
exert
therapeutic
effects
in
Alzheimer's
disease
(AD)
by
modulating
amyloid-β
(Aβ)
metabolism.
Meanwhile,
the
direct
interactions
between
GLP-1RAs
Aβ
their
functional
consequences
remain
unexplored.
In
this
study,
monomeric
Aβ40/Aβ42
of
GLP-1(7-37)
its
several
analogs
(semaglutide
(Sema),
liraglutide
(Lira),
exenatide
(Exen))
were
studied
using
biolayer
interferometry
surface
plasmon
resonance
spectroscopy.
The
quaternary
structure
was
investigated
dynamic
light
scattering.
on
fibrillation
assessed
thioflavin
T
assay
electron
microscopy.
impact
cytotoxicity
evaluated
via
MTT
assay.
Monomeric
Aβ40
Aβ42
directly
bind
to
GLP-1(7-37),
Sema,
Lira,
Exen,
with
highest
affinity
for
Lira
(the
lowest
estimates
equilibrium
dissociation
constants
42-60
nM).
are
prone
oligomerization,
which
may
affect
binding
Aβ.
Exen
inhibit
fibrillation,
whereas
Sema
promotes
it.
GLP-1
decrease
toward
SH-SY5Y
cells,
while
enhances
without
affecting
cytotoxic
effect
Aβ42.
Overall,
interact
differentially
modulate
cytotoxicity,
suggesting
need
further
our
observed
vivo.
Der Nervenarzt,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 5, 2025
Albiglutide,
dulaglutide,
exenatide,
liraglutide,
lixisenatide,
orforglipron
and
semaglutide
are
glucagon-like
peptide‑1
(GLP-1)
receptor
agonists.
Tirzepatide
targets
not
only
GLP‑1
but
also
glucose-dependent
insulinotropic
peptide
(GIP)
receptors
retatrutide
is
a
triple
GLP‑1,
GIP
glucagon
agonist.
The
agonists
increase
insulin
release
suppress
release.
They
slow
down
the
emptying
of
stomach
thus
prevent
blood
sugar
spikes.
reduce
appetite
food
intake.
In
brain
lead
to
better
glycemic
control
they
appear
have
anti-inflammatory
neuroprotective
effects.
It
has
been
reported
that
oxidative
stress
apoptosis,
lower
risk
ischemia
promote
neurogenesis.
can
influence
dopaminergic
signal
transduction
in
nucleus
accumbens.
Therefore,
could
modify
effect
cocaine,
alcohol
nicotine.
Preliminary
investigations
provide
indications
therapeutic
benefits
for
people
with
dementia,
eating
disorders,
psychopharmacologically
induced
weight
gain,
depression,
anxiety
substance
use
disorders.
Typical
accompanying
adverse
reactions
gastrointestinal
side
effects,
such
as
nausea,
vomiting,
diarrhea,
eructation
gastroesophageal
reflux.
More
severe
effects
include
pancreatitis,
allergic
reactions,
renal
function
disorders
possibly
an
increased
thyroid
cancer.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(8), P. 3905 - 3905
Published: April 21, 2025
Alzheimer's
disease
(AD)
is
a
prevalent
neurodegenerative
disorder
characterized
by
cognitive
impairments
such
as
memory
loss
and
executive
dysfunction.
The
primary
pathological
features
of
AD
include
the
deposition
amyloid-beta
(Aβ)
plaques,
hyperphosphorylation
tau
proteins
leading
to
neurofibrillary
tangles,
disruptions
neuronal
synaptic
functions,
chronic
inflammatory
responses.
These
multifactorial
interactions
drive
progression.
To
date,
various
therapeutic
agents
targeting
these
mechanisms
have
been
developed.
This
article
provides
comprehensive
review
pathogenesis
AD,
recent
advances
in
drug
development
different
pathways,
current
challenges,
future
directions,
aiming
offer
valuable
insights
for
clinical
treatment
research.
