Archiv der Pharmazie,
Год журнала:
2025,
Номер
358(4)
Опубликована: Апрель 1, 2025
ABSTRACT
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
characterized
by
progressive
onset
of
symptoms,
including
memory
loss,
accompanied
other
neurological
impairments.
This
progression
attributed
to
the
deterioration
neuronal
connections
and
decrease
in
neurotransmission.
Although
this
phenomenon
has
been
extensively
studied
cholinergic
system,
it
also
affects
neurobiological
pathways,
particularly
adrenergic
transmission.
In
context,
use
agonists,
particular,
β
2
‐adrenergic
receptor
(β
AR)
may
represent
promising
therapeutic
approach.
After
reviewing
main
pharmacological
aspects
related
these
receptors,
we
will
first
present
different
existing
modulators
their
peripheral
effects.
We
then
analyze
results
studies
investigating
models.
Finally,
discuss
conditions
prospects
for
development
new
treatment
using
AR
agonist.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 16, 2024
Abstract
The
human
gastrointestinal
tract
is
populated
with
a
diverse
microbial
community.
vast
genetic
and
metabolic
potential
of
the
gut
microbiome
underpins
its
ubiquity
in
nearly
every
aspect
biology,
including
health
maintenance,
development,
aging,
disease.
advent
new
sequencing
technologies
culture-independent
methods
has
allowed
researchers
to
move
beyond
correlative
studies
toward
mechanistic
explorations
shed
light
on
microbiome–host
interactions.
Evidence
unveiled
bidirectional
communication
between
central
nervous
system,
referred
as
“microbiota–gut–brain
axis”.
microbiota–gut–brain
axis
represents
an
important
regulator
glial
functions,
making
it
actionable
target
ameliorate
development
progression
neurodegenerative
diseases.
In
this
review,
we
discuss
mechanisms
As
provides
essential
cues
microglia,
astrocytes,
oligodendrocytes,
examine
communications
microbiota
these
cells
during
healthy
states
Subsequently,
diseases
using
metabolite-centric
approach,
while
also
examining
role
microbiota-related
neurotransmitters
hormones.
Next,
targeting
intestinal
barrier,
blood–brain
meninges,
peripheral
immune
system
counteract
dysfunction
neurodegeneration.
Finally,
conclude
by
assessing
pre-clinical
clinical
evidence
probiotics,
prebiotics,
fecal
transplantation
A
thorough
comprehension
will
foster
effective
therapeutic
interventions
for
management
Molecular Biomedicine,
Год журнала:
2023,
Номер
4(1)
Опубликована: Ноя. 8, 2023
Abstract
The
Janus
kinase-signal
transducer
and
transcription
activator
pathway
(JAK-STAT)
serves
as
a
cornerstone
in
cellular
signaling,
regulating
physiological
pathological
processes
such
inflammation
stress.
Dysregulation
this
can
lead
to
severe
immunodeficiencies
malignancies,
its
role
extends
neurotransduction
pro-inflammatory
signaling
mechanisms.
Although
JAK
inhibitors
(Jakinibs)
have
successfully
treated
immunological
inflammatory
disorders,
their
application
has
generally
been
limited
diseases
with
similar
pathogenic
features.
Despite
the
modest
expression
of
JAK-STAT
CNS,
it
is
crucial
for
functions
cortex,
hippocampus,
cerebellum,
making
relevant
conditions
like
Parkinson's
disease
other
neuroinflammatory
disorders.
Furthermore,
influence
on
serotonin
receptors
phospholipase
C
implications
stress
mood
This
review
expands
understanding
JAK-STAT,
moving
beyond
traditional
contexts
explore
stress-related
disorders
CNS
function.
Recent
findings,
effectiveness
Jakinibs
chronic
rheumatoid
arthritis,
expand
therapeutic
applicability.
Advances
isoform-specific
inhibitors,
including
filgotinib
upadacitinib,
promise
greater
specificity
fewer
off-target
effects.
Combination
therapies,
involving
monoclonal
antibodies,
aiming
enhance
efficacy
also
give
great
hope.
Overall,
bridges
gap
between
basic
science
clinical
application,
elucidating
complex
human
health
guiding
future
interventions.
Graphical
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Июнь 8, 2024
Abstract
Pain
is
estimated
to
affect
more
than
20%
of
the
global
population,
imposing
incalculable
health
and
economic
burdens.
Effective
pain
management
crucial
for
individuals
suffering
from
pain.
However,
current
methods
assessment
treatment
fall
short
clinical
needs.
Benefiting
advances
in
neuroscience
biotechnology,
neuronal
circuits
molecular
mechanisms
critically
involved
modulation
have
been
elucidated.
These
research
achievements
incited
progress
identifying
new
diagnostic
therapeutic
targets.
In
this
review,
we
first
introduce
fundamental
knowledge
about
pain,
setting
stage
subsequent
contents.
The
review
next
delves
into
underlying
disorders,
including
gene
mutation,
epigenetic
modification,
posttranslational
inflammasome,
signaling
pathways
microbiota.
To
better
present
a
comprehensive
view
research,
two
prominent
issues,
sexual
dimorphism
comorbidities,
are
discussed
detail
based
on
findings.
status
quo
evaluation
manipulation
summarized.
A
series
improved
innovative
strategies,
such
as
therapy,
monoclonal
antibody,
brain-computer
interface
microbial
intervention,
making
strides
towards
application.
We
highlight
existing
limitations
future
directions
enhancing
quality
preclinical
research.
Efforts
decipher
complexities
pathology
will
be
instrumental
translating
scientific
discoveries
practice,
thereby
improving
bench
bedside.
The Innovation,
Год журнала:
2025,
Номер
6(3), С. 100774 - 100774
Опубликована: Янв. 18, 2025
Traditional
medicines
serve
not
only
as
an
integral
part
of
medical
treatments
prescribed
by
healthcare
providers
but
also
a
fundamental
reservoir
for
novel
molecular
scaffolds.
However,
gaps
remain
in
our
understanding
the
mechanisms
underlying
their
activity.
A
superfamily
membrane
proteins,
G
protein-coupled
receptors
(GPCRs),
have
been
demonstrated
to
be
potential
targets
several
compounds
isolated
from
traditional
medicines.
Given
that
GPCRs
approximately
one-third
all
marketed
drugs,
they
may
compelling
repurposing
Despite
this
potential,
research
investigating
activity
or
ligands
across
GPCRome,
library
human
GPCRs,
is
scarce.
Drawing
on
functional
and
structural
knowledge
presently
available,
review
contemplates
prospective
trends
GPCR
drug
discovery,
proposes
innovative
strategies
medicines,
highlights
ligand
screening
approaches
identifying
drug-like
molecules.
To
discover
bioactive
molecules
either
directly
bind
indirectly
modify
function,
genome-wide
pan-GPCR
discovery
platform
was
designed
identification
components
targets,
evaluation
pharmacological
profiles.
This
aims
aid
exploration
all-sided
relations
between
GPCRome
using
advanced
high-throughput
techniques.
We
present
various
used
many,
including
ourselves,
illuminate
previously
unexplored
aspects
GPCRs.
Molecular Biomedicine,
Год журнала:
2023,
Номер
4(1)
Опубликована: Дек. 4, 2023
G
protein-coupled
receptors
(GPCRs)
are
versatile
and
vital
proteins
involved
in
a
wide
array
of
physiological
processes
responses,
such
as
sensory
perception
(e.g.,
vision,
taste,
smell),
immune
response,
hormone
regulation,
neurotransmission.
Their
diverse
essential
roles
the
body
make
them
significant
focus
for
pharmaceutical
research
drug
development.
Currently,
approximately
35%
marketed
drugs
directly
target
GPCRs,
underscoring
their
prominence
therapeutic
targets.
Recent
advances
structural
biology
have
substantially
deepened
our
understanding
GPCR
activation
mechanisms
interactions
with
G-protein
arrestin
signaling
pathways.
This
review
offers
an
in-depth
exploration
both
traditional
recent
methods
structure
analysis.
It
presents
structure-based
insights
into
ligand
recognition
receptor
delves
deeper
canonical
noncanonical
pathways
downstream
GPCRs.
Furthermore,
it
highlights
advancements
GPCR-related
discovery
Particular
emphasis
is
placed
on
selective
drugs,
allosteric
biased
signaling,
polyphamarcology,
antibody
drugs.
Our
goal
to
provide
researchers
thorough
updated
determination,
pathway
investigation,
foundation
aims
propel
forward-thinking
approaches
that
drawing
upon
latest
selectivity,
activation,
mechanisms.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(7), С. 831 - 831
Опубликована: Июнь 25, 2024
Histamine
performs
dual
roles
as
an
immune
regulator
and
a
neurotransmitter
in
the
mammalian
brain.
The
histaminergic
system
plays
vital
role
regulation
of
wakefulness,
cognition,
neuroinflammation,
neurogenesis
that
are
substantially
disrupted
various
neurodegenerative
neurodevelopmental
disorders.
H3
receptor
(H3R)
antagonists
inverse
agonists
potentiate
endogenous
release
brain
histamine
have
been
shown
to
enhance
cognitive
abilities
animal
models
several
Microglial
activation
subsequent
neuroinflammation
implicated
impacting
embryonic
adult
neurogenesis,
contributing
development
Alzheimer's
disease
(AD),
Parkinson's
(PD),
autism
spectrum
disorder
(ASD).
Acknowledging
importance
microglia
both
neurodevelopment,
well
their
by
histamine,
offers
intriguing
therapeutic
target
for
these
inhibition
H3Rs
has
found
facilitate
shift
from
proinflammatory
M1
state
anti-inflammatory
M2
state,
leading
reduction
activity
microglial
cells.
Also,
pharmacological
studies
demonstrated
H3R
showed
positive
effects
reducing
biomarkers,
suggesting
potential
simultaneously
modulating
crucial
neurotransmissions
signaling
cascades
such
PI3K/AKT/GSK-3β
pathway.
In
this
review,
we
highlight
addressing
pathology
decline
disorders,
e.g.,
AD,
PD,
ASD,
with
inflammatory
component.
ACS Pharmacology & Translational Science,
Год журнала:
2025,
Номер
8(2), С. 271 - 285
Опубликована: Янв. 8, 2025
Astrocytes
are
a
type
of
glial
cell
that
involved
in
actively
modulating
synaptic
plasticity,
neurotransmitter
homeostasis,
and
neuroinflammatory
responses.
More
importantly,
they
coordinate
neuronal
activity
cerebral
blood
flow
(CBF)
what
is
known
as
neurovascular
coupling
(NVC).
NVC
an
essential
mechanism
maintains
the
high
energy
demand
brain
requires
by
supplying
continuous
rapid
supply
oxygen
nutrients
through
CBF.
Impairment
one
key
events
triggers
spiral
occurrences
lead
to
clinical
advancement
Alzheimer's
disease
(AD).
It
yet
be
determined
molecular
manifestations
impairment
relate
to;
nonetheless,
it
believed
alterations
G
protein-coupled
receptors
(GPCRs)
responsible
for
exacerbating
these
effects.
In
this
review,
we
summarize
current
evidence
supporting
involvement
GPCRs
on
astrocytes
pathophysiology
AD.
Additionally,
propose
potential
research
directions
further
elucidate
underlying
mechanisms
evaluate
feasibility
targeting
specific
therapeutic
strategy
correct
memory
impairments
associated
with
