Biomolecules,
Journal Year:
2024,
Volume and Issue:
14(7), P. 872 - 872
Published: July 19, 2024
Glucagon-like
peptide-1
(GLP-1)-based
drugs
have
been
approved
by
the
United
States
Food
and
Drug
Administration
(FDA)
are
widely
used
to
treat
type
2
diabetes
mellitus
(T2DM)
obesity.
More
recent
developments
of
unimolecular
peptides
targeting
multiple
incretin-related
receptors
("multi-agonists"),
including
glucose-dependent
insulinotropic
polypeptide
(GIP)
receptor
(GIPR)
glucagon
(Gcg)
(GcgR),
emerged
with
aim
enhancing
drug
benefits.
In
this
study,
we
utilized
human
mouse
microglial
cell
lines,
HMC3
IMG,
respectively,
together
neuroblastoma
SH-SY5Y
line
as
cellular
models
neurodegeneration.
Using
these
studied
neuroprotective
anti-inflammatory
capacity
several
multi-agonists
in
comparison
a
single
GLP-1
(GLP-1R)
agonist,
exendin-4.
Our
data
demonstrate
that
two
selected
GLP-1R/GIPR
dual
agonists
GLP-1R/GIPR/GcgR
triple
agonist
not
only
neurotrophic
effects
but
also
anti-neuroinflammatory
properties,
indicated
decreased
cyclooxygenase
(COX2)
expression,
nitrite
production,
pro-inflammatory
cytokine
release.
addition,
our
results
indicate
potential
outperform
commercially
available
GLP-1R
neurodegenerative
disease
treatment.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(10), P. 8498 - 8498
Published: May 9, 2023
For
many
decades
after
their
discovery,
astrocytes,
the
abundant
glial
cells
of
brain,
were
believed
to
work
as
a
glue,
supporting
structure
and
metabolic
functions
neurons.
A
revolution
that
started
over
30
years
ago
revealed
additional
these
cells,
including
neurogenesis,
gliosecretion,
glutamate
homeostasis,
assembly
function
synapses,
neuronal
metabolism
with
energy
production,
others.
These
properties
have
been
confirmed,
limited
however,
proliferating
astrocytes.
During
aging
or
following
severe
brain
stress
lesions,
astrocytes
are
converted
into
no-longer-proliferating,
senescent
forms,
similar
in
morphology
but
profoundly
modified
functions.
The
changed
specificity
is
largely
due
altered
gene
expression.
ensuing
effects
include
downregulation
typical
upregulation
others,
concerned
neuroinflammation,
release
pro-inflammatory
cytokines,
dysfunction
etc.,
specific
senescence
program.
decrease
support
protection
by
induces
development,
vulnerable
regions,
toxicity
together
cognitive
decline.
Similar
changes,
ultimately
reinforced
astrocyte
aging,
also
induced
traumatic
events
molecules
involved
dynamic
processes.
Senescent
play
critical
roles
development
diseases.
first
demonstration,
obtained
for
Alzheimer’s
disease
less
than
10
ago,
contributed
elimination
previously
predominant
neuro-centric
amyloid
hypothesis.
initial
effects,
operating
considerable
time
before
appearance
known
symptoms
evolve
severity
up
proliferation
during
final
outcome.
Involvement
other
neurodegenerative
diseases
cancer
now
intensely
investigated.
Nutrients,
Journal Year:
2023,
Volume and Issue:
15(21), P. 4556 - 4556
Published: Oct. 27, 2023
Diabetes
affects
one
in
eleven
adults
globally,
with
rising
cases
the
past
30
years.
Type
1
and
type
2
cause
blood
sugar
problems,
increasing
cardiovascular
risks.
Dietary
control,
including
chickpeas,
is
suggested
but
needs
more
research.
Comprehensive
searches
were
conducted
across
multiple
databases
for
randomized
controlled
trial
efficacy
of
chickpea
consumption
to
lower
levels
a
healthy
range,
data
extraction
risk
bias
assessment
performed
independently
by
two
researchers.
Statistical
analysis
was
using
RevMan
5.4,
expressing
continuous
as
mean
differences
ratios
95%
confidence
intervals,
summary
findings
provided
considering
variations
study
characteristics.
A
total
118
articles
initially
identified
from
seven
databases,
primarily
Anglo–American
countries,
resulting
12
selected
studies
after
identification
screening
processes.
These
involved
182
participants,
focusing
on
or
normoglycemic
adults,
assessed
effects
chickpeas
compared
various
foods
such
wheat,
potatoes,
pasta,
sauce,
cheese,
rice,
corn.
meta-analysis
involving
subset
demonstrated
that
effective
reducing
glucose
iAUC
potatoes
wheat.
Chickpeas
offer
potential
control
through
low
starch
digestibility,
high
fiber,
protein,
hormonal
effects.
Although
insulin
benefits
are
seen,
statistical
significance
varies,
supporting
their
role
diabetic
diets
nutrient-rich
over
processed
carbs.
Journal of Alzheimer s Disease,
Journal Year:
2024,
Volume and Issue:
101(s1), P. S317 - S343
Published: Oct. 18, 2024
Functional
impairments
in
the
brain's
insulin
and
insulin-like
growth
factor
(IGF)
signal
transduction
networks
are
recognized
mediators
of
dysregulated
energy
metabolism,
a
major
driver
Alzheimer's
disease
(AD)
neurodegeneration
cascade.
AD-associated
insulin-deficient
insulin-resistant
states
mimic
those
diabetes
mellitus
affect
all
cell
types
brain.
Besides
accounting
for
abundant
amyloid-β
hyperphosphorylated
tau
lesions
AD,
insulin/IGF
pathway
dysfunctions
cause
cortical
atrophy,
loss
synaptic
plasticity,
white
matter
myelin/oligodendrocyte
degeneration,
astrocyte
microglial
neuroinflammation
oxidative
stress,
deficits
mitochondrial
dysfunction,
microvascular
disease.
These
same
neuropathological
processes
have
been
linked
to
cognitive
impairment
type
2
mellitus,
Parkinson's
disease,
vascular
dementia.
Strategies
address
metabolic
borrowed
from
other
diseases
leveraged
on
preclinical
AD
model
data.
The
repurposing
drugs
led
clinical
trials
with
intranasal
insulin,
followed
by
sensitizers
including
metformin
peroxisome-proliferator-activated
receptor
agonists,
then
incretin
mimetics
primarily
targeting
GLP-1
receptors.
In
addition,
glucose-lowering
agents
tested
their
efficacy
preventing
declines.
strengths
limitations
these
approaches
discussed.
main
conclusion
this
review
is
that
we
now
arrived
at
stage
which
it
time
long-term
trophic
availability
responsiveness,
signaling
abnormalities
extend
beyond
include
IGFs
interconnected
pathways,
need
multi-pronged
rather
than
single-pronged
therapeutic
remediate
forms
neurodegeneration.
Biomolecules,
Journal Year:
2024,
Volume and Issue:
14(7), P. 872 - 872
Published: July 19, 2024
Glucagon-like
peptide-1
(GLP-1)-based
drugs
have
been
approved
by
the
United
States
Food
and
Drug
Administration
(FDA)
are
widely
used
to
treat
type
2
diabetes
mellitus
(T2DM)
obesity.
More
recent
developments
of
unimolecular
peptides
targeting
multiple
incretin-related
receptors
("multi-agonists"),
including
glucose-dependent
insulinotropic
polypeptide
(GIP)
receptor
(GIPR)
glucagon
(Gcg)
(GcgR),
emerged
with
aim
enhancing
drug
benefits.
In
this
study,
we
utilized
human
mouse
microglial
cell
lines,
HMC3
IMG,
respectively,
together
neuroblastoma
SH-SY5Y
line
as
cellular
models
neurodegeneration.
Using
these
studied
neuroprotective
anti-inflammatory
capacity
several
multi-agonists
in
comparison
a
single
GLP-1
(GLP-1R)
agonist,
exendin-4.
Our
data
demonstrate
that
two
selected
GLP-1R/GIPR
dual
agonists
GLP-1R/GIPR/GcgR
triple
agonist
not
only
neurotrophic
effects
but
also
anti-neuroinflammatory
properties,
indicated
decreased
cyclooxygenase
(COX2)
expression,
nitrite
production,
pro-inflammatory
cytokine
release.
addition,
our
results
indicate
potential
outperform
commercially
available
GLP-1R
neurodegenerative
disease
treatment.
