ChemistrySelect,
Journal Year:
2025,
Volume and Issue:
10(6)
Published: Feb. 1, 2025
Abstract
The
pathogenesis
of
Alzheimer's
disease
(AD)
is
multifaceted,
and
more
than
one
factor
deemed
responsible
for
its
genesis
progression.
Hence,
the
multi‐target
approach
seems
plausible
en
route
to
development
therapeutics
targeting
in
particular,
other
neurological
disorders,
general.
Among
major
factors
AD
are
acetylcholinesterase
monoamine
oxidase
enzymes.
Acetylcholine
an
important
neurotransmitter
that
plays
a
role
processing
memory
learning.
Deficiency
this
observed
patients
AD;
largely
attributed
increased
expression
enzyme
(AChE)
breakdown
acetylcholine
neurotransmitter.
inhibitors
AChE
can
prevent
excessive
Monoamine
oxidases
brain
hydrolyzing
neurotransmitters
such
as
serotonin
dopamine
(among
others),
abnormally
rapid
hydrolysis
these
via
over‐activation
associated
with
several
neurodegenerative
disorders
including
anxiety
Parkinson's
disease.
Herein,
we
synthesized
focused
library
1,4‐dihydropyrimidines
(40
compounds)
using
deep
eutectic
solvent
evaluated
their
potential
inhibit
cholinesterase
(AChE
BChE)
(MAO
A
MAO
B)
Several
selective
highly
potent
were
identified;
silico
molecular
docking
dynamics
simulation
studies
helped
rationalize
binding
site
interactions
establish
useful
structure
activity
relationship.
In
ADME
prediction
data
identified
few
could
cross
blood‐brain
barrier,
compound
was
selected
vivo
estimation
LD
50
value
toxicity
mice,
skin
allergy
test
also
carried
out.
All
tests
established
safety
profile
compound.
results
encouraging
enough
further
pursue
DHPMs
promising
directed
ligands
against
disorders.
Journal of Biomechanical Engineering,
Journal Year:
2024,
Volume and Issue:
146(6)
Published: Feb. 29, 2024
Abstract
Numerical
and
analytical
solutions
were
employed
to
calculate
the
radius
of
an
amyloid-β
(Aβ)
plaque
over
time.
To
author's
knowledge,
this
study
presents
first
model
simulating
growth
Aβ
plaques.
Findings
indicate
that
can
attain
a
diameter
50
μm
after
20
years
growth,
provided
monomer
degradation
machinery
is
malfunctioning.
A
mathematical
incorporates
nucleation
autocatalytic
processes
using
Finke–Watzky
model.
The
resulting
system
ordinary
differential
equations
was
solved
numerically,
for
simplified
case
infinitely
long
half-life,
solution
found.
Assuming
aggregates
stick
together
distance
between
plaques
as
input
parameter
model,
it
possible
from
concentration
aggregates.
This
led
“cube
root
hypothesis,”
positing
size
increases
proportionally
cube
hypothesis
helps
explain
why
larger
grow
more
slowly.
Furthermore,
obtained
results
suggest
independent
kinetic
constants
governing
agglomeration,
indicating
kinetics
agglomeration
not
limiting
factor
growth.
Instead,
rate
limited
by
rates
production
degradation.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 6901 - 6901
Published: June 24, 2024
Alzheimer's
disease
(AD)
is
the
most
prevalent
neurodegenerative
disorder
and
affects
millions
of
individuals
globally.
AD
associated
with
cognitive
decline
memory
loss
that
worsens
aging.
A
statistical
report
using
U.S.
data
on
estimates
approximately
6.9
million
suffer
from
AD,
a
number
projected
to
surge
13.8
by
2060.
Thus,
there
critical
imperative
pinpoint
address
its
hallmark
tau
protein
aggregation
early
prevent
manage
debilitating
effects.
Amyloid-β
proteins
are
primarily
formation
plaques
neurofibril
tangles
in
brain.
Current
research
efforts
focus
degrading
amyloid-β
or
inhibiting
their
synthesis,
particularly
targeting
APP
processing
hyperphosphorylation,
aiming
develop
effective
clinical
interventions.
However,
navigating
this
intricate
landscape
requires
ongoing
studies
trials
treatments
truly
make
difference.
Genome-wide
association
(GWASs)
across
various
cohorts
identified
40
loci
over
300
genes
AD.
Despite
wealth
genetic
data,
much
remains
be
understood
about
functions
these
role
process,
prompting
continued
investigation.
By
delving
deeper
into
associations,
novel
targets
such
as
kinases,
proteases,
cytokines,
degradation
pathways,
offer
new
directions
for
drug
discovery
therapeutic
intervention
This
review
delves
biological
pathways
disrupted
identifies
how
variations
within
could
serve
potential
treatment
strategies.
Through
comprehensive
understanding
molecular
underpinnings
researchers
aim
pave
way
more
therapies
can
alleviate
burden
devastating
disease.
Journal of Clinical Medicine,
Journal Year:
2024,
Volume and Issue:
13(2), P. 403 - 403
Published: Jan. 11, 2024
Limitations
of
pharmaceutical
drugs
and
biologics
for
chronic
diseases
(e.g.,
medication
non-adherence,
adverse
effects,
toxicity,
or
inadequate
efficacy)
can
be
mitigated
by
mobile
medical
apps,
known
as
digital
therapeutics
(DTx).
Authorization
adjunct
DTx
the
US
Food
Drug
Administration
draft
guidelines
on
“prescription
drug
use-related
software”
illustrate
opportunities
to
create
+
combination
therapies,
ultimately
leading
towards
drug–device
products
(DTx
has
a
status
devices).
Digital
interventions
(mobile,
web-based,
virtual
reality,
video
game
applications)
demonstrate
clinically
meaningful
benefits
people
living
with
Alzheimer’s
disease,
dementia,
rheumatoid
arthritis,
cancer,
pain,
epilepsy,
depression,
anxiety.
In
respective
animal
disease
models,
preclinical
studies
environmental
enrichment
other
non-pharmacological
modalities
(physical
activity,
social
interactions,
learning,
music)
surrogates
“active
ingredients”
also
show
improved
outcomes.
this
narrative
review,
we
discuss
how
therapies
impact
translational
research,
discovery
development,
generic
repurposing,
gene
therapies.
Market-driven
incentives
are
illustrated
Humira®
(adalimumab)
facing
“patent-cliff”
competition
cheaper
more
effective
biosimilars
seamlessly
integrated
DTx.
conclusion,
pharma
biotech
companies,
patients,
healthcare
professionals
will
benefit
from
accelerating
integration
pharmacotherapies.
ACS Pharmacology & Translational Science,
Journal Year:
2025,
Volume and Issue:
8(2), P. 271 - 285
Published: Jan. 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
Phytotherapy Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 15, 2025
Alzheimer's
disease
(AD)
is
a
type
of
neurodegenerative
illness
in
which
β-amyloid
(Aβ)
and
tau
protein
accumulate
neurons
the
form
tangles.
The
pathophysiological
pathway
AD
consists
Aβ-amyloid
peptides,
proteins,
oxidative
stress
increased
neuro-inflammatory
response.
Food
Drug
Administration
United
States
has
authorized
various
drugs
for
effective
treatment
AD,
include
galantamine,
rivastigmine,
donepezil,
memantine,
sodium
oligomannate,
lecanemab,
aducanumab.
major
disadvantage
these
that
they
only
provide
"symptomatic"
relief.
They
are
most
early
stages
or
mild
to
moderate
cases
disease,
but
not
suitable
long-term
use.
Besides
conventional
therapies,
phytochemicals
have
potential
stop
progression
AD.
According
research,
use
against
gained
attention
due
their
potent
anti-inflammatory,
antioxidant,
anti-hyperphosphorylation
protein,
metal
chelation,
anti-amyloid
properties.
This
study
seeks
an
up-to-date
compilation
current
promising
breakthroughs
therapy
using
phytochemicals.
It
could
be
concluded
light
serve
as
However,
more
mechanistic
investigations
needed
determine
clinical
implications
treatment.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
175, P. 116784 - 116784
Published: May 22, 2024
1,8-Cineole
is
a
bicyclic
monoterpene
widely
distributed
in
the
essential
oils
of
various
medicinal
plants,
and
it
exhibits
significant
anti-inflammatory
antioxidant
activities.
We
aimed
to
investigate
therapeutic
effect
1,8-cineole
on
anti-Alzheimer's
disease
by
using
transgenic
Caenorhabditis
elegans
models.
Our
studies
demonstrated
that
significantly
relieved
Aβ1–42-induced
paralysis
exhibited
remarkable
anti-Aβ1–42
aggregation
activities
nematodes
CL4176,
CL2006
CL2355.
developed
1,8-cineole/cyclodextrin
inclusion
complex,
displaying
enhanced
anti-paralysis,
anti-Aβ
compared
1,8-cineole.
In
addition,
we
found
treatment
activated
SKN-1/Nrf-2
pathway
induced
autophagy
nematodes.
results
1,8-cineole,
which
provide
potential
approach
for
Alzheimer's
disease.
Ageing Research Reviews,
Journal Year:
2024,
Volume and Issue:
99, P. 102383 - 102383
Published: June 30, 2024
Globally,
Alzheimer's
disease
(AD)
is
the
most
widespread
chronic
neurodegenerative
disorder,
leading
to
cognitive
impairment,
such
as
aphasia
and
agnosia,
well
mental
symptoms,
like
behavioral
abnormalities,
that
place
a
heavy
psychological
financial
burden
on
families
of
afflicted.
Unfortunately,
no
particular
medications
exist
treat
AD,
current
treatments
only
impede
its
progression.The
link
between
AD
type
2
diabetes
(T2D)
has
been
increasingly
revealed
by
research;
danger
developing
both
T2D
rises
exponentially
with
age,
being
especially
prone
AD.
This
propelled
researchers
investigate
mechanism(s)
underlying
this
connection.
A
critical
review
relationship
insulin
resistance,
Aβ,
oxidative
stress,
mitochondrial
hypothesis,
abnormal
phosphorylation
Tau
protein,
inflammatory
response,
high
blood
glucose
levels,
neurotransmitters
signaling
pathways,
vascular
issues
in
diabetes,
similarities
two
diseases,
presented
review.
Grasping
essential
mechanisms
behind
detrimental
interaction
may
offer
chances
devise
successful
therapeutic
strategies.
