CNS Drugs,
Год журнала:
2023,
Номер
37(7), С. 599 - 637
Опубликована: Июнь 21, 2023
Even
though
language
is
essential
in
human
communication,
research
on
pharmacological
therapies
for
deficits
highly
prevalent
neurodegenerative
and
vascular
brain
diseases
has
received
little
attention.
Emerging
scientific
evidence
suggests
that
disruption
of
the
cholinergic
system
may
play
an
role
associated
with
Alzheimer's
disease
cognitive
impairment,
including
post-stroke
aphasia.
Therefore,
current
models
processing
are
beginning
to
appraise
implications
modulator
acetylcholine
functions.
Future
work
should
be
directed
further
analyze
interplay
between
language,
focusing
identifying
regions
receiving
innervation
susceptible
modulation
pharmacotherapy
improve
affected
domains.
The
evaluation
trials
impairment
thus
far
been
limited
coarse-grained
methods.
More
precise,
fine-grained
testing
needed
refine
patient
selection
detect
subtle
initial
phases
decline.
Additionally,
noninvasive
biomarkers
can
help
identify
depletion.
However,
despite
investigation
treatment
data
its
effectiveness
insufficient
controversial.
In
case
aphasia,
agents
showing
promise,
particularly
when
combined
speech-language
therapy
promote
trained-dependent
neural
plasticity.
explore
potential
benefits
investigate
optimal
strategies
combining
these
other
therapeutic
approaches.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 15
Опубликована: Фев. 8, 2024
Alzheimer's
disease
(AD)
is
a
progressive
neurological
disorder
responsible
for
the
cognitive
dysfunction
and
impairment
in
patients.
Acetylcholinesterase
inhibitors
(AChEIs)
are
used
to
treat
AD
however,
these
only
provided
symptomatic
relief
more
efficient
drug
molecules
desired
effective
treatment
of
disease.
In
this
article,
ligand-based
drug-designing
strategy
was
develop
validate
field-based
3D-QSAR
pharmacophore
model
on
quinazoline-based
AChEIs
reported
literature.
The
validated
(AAAHR_1)
as
prefilter
screen
an
ASINEX
database
via
virtual
screening
workflow
(VSW).
hits
generated
were
subjected
MM-GBSA
identify
potential
top
three
scoring
(BAS
05264565,
LEG
12727144
SYN
22339886)
evaluated
thermodynamic
stability
at
target
site
using
molecular
dynamic
simulations.
Additionally,
DFT
study
performed
predict
reactivity
lead
towards
acetylcholinesterase
(AChE).
Thus,
by
utilising
various
computational
tools,
identified
potent
that
can
be
developed
candidates
AD.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 1816 - 1816
Опубликована: Фев. 20, 2025
There
is
still
a
lack
of
effective
therapies
for
Alzheimer's
disease
(AD),
the
leading
cause
dementia
and
cognitive
decline.
Identifying
reliable
biomarkers
therapeutic
targets
crucial
advancing
AD
research.
In
this
study,
we
developed
an
aggregative
multi-filter
gene
selection
approach
to
identify
biomarkers.
This
method
integrates
hub
ranking
techniques,
such
as
degree
bottleneck,
with
feature
algorithms,
including
Random
Forest
Double
Input
Symmetrical
Relevance,
applies
aggregation
improve
accuracy
robustness.
Five
publicly
available
AD-related
microarray
datasets
(GSE48350,
GSE36980,
GSE132903,
GSE118553,
GSE5281),
covering
diverse
brain
regions
like
hippocampus
frontal
cortex,
were
analyzed,
yielding
803
overlapping
differentially
expressed
genes
from
464
492
normal
cases.
An
independent
dataset
(GSE109887)
was
used
external
validation.
The
identified
50
prioritized
genes,
achieving
AUC
86.8
in
logistic
regression
on
validation
dataset,
highlighting
their
predictive
value.
Pathway
analysis
revealed
involvement
critical
biological
processes
synaptic
vesicle
cycles,
neurodegeneration,
function.
These
findings
provide
insights
into
potential
AD.
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Май 14, 2025
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
characterized
by
cognitive
decline,
amyloid-beta
(Aβ)
aggregation,
tau
pathology,
and
chronic
neuroinflammation.
Among
these,
neuroinflammation
plays
crucial
role
in
exacerbating
progression,
making
it
an
attractive
therapeutic
target.
However,
the
presence
of
blood-brain
barrier
(BBB)
significantly
limits
effective
delivery
agents
to
brain,
necessitating
novel
drug
strategies.
Nanocarrier-based
systems
have
emerged
as
promising
solution
these
challenges,
offering
targeted
transport,
enhanced
BBB
penetration,
improved
bioavailability
while
minimizing
systemic
toxicity.
This
review
explores
current
advancements
nanocarrier-mediated
for
AD,
focusing
on
mechanisms
neuroinflammation,
nanocarriers
overcoming
BBB,
their
ability
modulate
inflammatory
pathways.
Furthermore,
discusses
preclinical
validation
strategies
key
including
safety
concerns,
large-scale
production
limitations,
regulatory
hurdles
that
must
be
addressed
enable
clinical
translation.
Future
perspectives
emphasize
integration
nanotechnology
with
precision
medicine,
gene
therapy,
artificial
intelligence
optimize
nanocarrier
design
individualized
AD
treatment.
By
obstacles,
hold
potential
revolutionize
approaches
other
diseases.
PLoS ONE,
Год журнала:
2025,
Номер
20(5), С. e0320789 - e0320789
Опубликована: Май 20, 2025
Alzheimer’s
disease
(AD)
causes
a
progressive
decline
in
memory,
along
with
impairments
other
cognitive
abilities.
The
main
pharmacological
target
for
treatment
is
acetylcholinesterase
(AChE),
biochemical
enzyme
belonging
to
the
cholinesterase
(ChE)
family.
In
search
novel
hit
compoundswith
potential
as
future
Alzheimer's
therapies,
series
of
carbamates
derivatives
were
designed
and
evaluated
using
computational
approaches
including
QSAR
modeling,
molecular
docking,
ADMET
profiling,
dynamics
simulations.
following
study
focused
on
development
model
satisfactory
statistical
properties.
analysis
ligands,
demonstrated
good
pharmacokinetic
Molecular
docking
identified
M6
promising
AChE
binder
score
-11.200
kcal/mol,
while
Donepezil
control
returned
-10.800
kcal/mol.
validity
docked
complex
was
confirmed
simulations,
where
trajectory
plots
found
be
stable
consistent
over
100
ns
intervals.
enclosed
highlights
chemical
starting
point
(CSP)
(i.e.,
compound)
targeting
therapeutic
strategy
against
AD.