Epilepsy & Behavior,
Journal Year:
2022,
Volume and Issue:
129, P. 108609 - 108609
Published: Feb. 14, 2022
Epilepsy,
sleep,
and
Alzheimer's
disease
(AD)
are
tightly
potentially
causally
interconnected.
The
aim
of
our
review
was
to
investigate
current
research
directions
on
these
relationships.
Our
hope
is
that
they
may
indicate
preventive
measures
new
treatment
options
for
early
neurodegeneration.
We
included
articles
assessed
all
three
topics
were
published
during
the
last
ten
years.
found
this
literature
corroborates
connections
various
pathophysiological
levels,
including
sleep-stage-related
epileptiform
activity
in
AD,
negative
consequences
different
sleep
disorders
epilepsy
cognition,
common
biochemical
pathways
as
well
network
dysfunctions.
Here
we
provide
a
detailed
overview
discuss
promising
diagnostic
therapeutic
consequences.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Aug. 23, 2024
Abstract
Alzheimer’s
disease
(AD)
stands
as
the
predominant
form
of
dementia,
presenting
significant
and
escalating
global
challenges.
Its
etiology
is
intricate
diverse,
stemming
from
a
combination
factors
such
aging,
genetics,
environment.
Our
current
understanding
AD
pathologies
involves
various
hypotheses,
cholinergic,
amyloid,
tau
protein,
inflammatory,
oxidative
stress,
metal
ion,
glutamate
excitotoxicity,
microbiota-gut-brain
axis,
abnormal
autophagy.
Nonetheless,
unraveling
interplay
among
these
pathological
aspects
pinpointing
primary
initiators
require
further
elucidation
validation.
In
past
decades,
most
clinical
drugs
have
been
discontinued
due
to
limited
effectiveness
or
adverse
effects.
Presently,
available
primarily
offer
symptomatic
relief
often
accompanied
by
undesirable
side
However,
recent
approvals
aducanumab
(
1
)
lecanemab
2
Food
Drug
Administration
(FDA)
present
potential
in
disrease-modifying
Nevertheless,
long-term
efficacy
safety
need
Consequently,
quest
for
safer
more
effective
persists
formidable
pressing
task.
This
review
discusses
pathogenesis,
advances
diagnostic
biomarkers,
latest
updates
trials,
emerging
technologies
drug
development.
We
highlight
progress
discovery
selective
inhibitors,
dual-target
allosteric
modulators,
covalent
proteolysis-targeting
chimeras
(PROTACs),
protein-protein
interaction
(PPI)
modulators.
goal
provide
insights
into
prospective
development
application
novel
drugs.
Life,
Journal Year:
2021,
Volume and Issue:
11(1), P. 28 - 28
Published: Jan. 6, 2021
Although
the
mechanisms
of
toxic
activity
tau
are
not
fully
recognized,
it
is
supposed
that
toxicity
related
rather
to
insoluble
aggregates
but
its
intermediate
forms.
It
seems
neurofibrillar
tangles
(NFTs)
themselves,
despite
being
composed
tau,
probably
neither
necessary
nor
sufficient
for
tau-induced
neuronal
dysfunction
and
toxicity.
Tau
oligomers
(TauOs)
formed
during
early
stages
aggregation
pathological
forms
play
a
key
role
in
eliciting
loss
neurons
behavioral
impairments
several
neurodegenerative
disorders
called
tauopathies.
They
can
be
found
tauopathic
diseases,
most
common
which
Alzheimer’s
disease
(AD).
Evidence
co-occurrence
b-amyloid,
α-synuclein,
into
their
forms,
i.e.,
oligomers,
suggests
these
species
interact
influence
each
other’s
The
mechanism
responsible
oligomeric
neurotoxicity
subject
intensive
investigation.
In
this
review,
we
summarize
recent
literature
on
damaging
effect
TauOs
stability
genome
function
nucleus,
energy
production
mitochondrial
function,
cell
signaling
synaptic
plasticity,
microtubule
assembly,
cytoskeleton
axonal
transport,
effectiveness
protein
degradation
system.
Molecular Neurodegeneration,
Journal Year:
2021,
Volume and Issue:
16(1)
Published: Nov. 6, 2021
Abstract
Multi-pathway
approaches
for
the
treatment
of
complex
polygenic
disorders
are
emerging
as
alternatives
to
classical
monotarget
therapies
and
microRNAs
particular
interest
in
that
regard.
MicroRNA
research
has
come
a
long
way
from
their
initial
discovery
cumulative
appreciation
regulatory
potential
healthy
diseased
brain.
However,
systematic
interrogation
putative
therapeutic
or
toxic
effects
(models
of)
Alzheimer’s
disease
is
currently
missing
fundamental
findings
yet
be
translated
into
clinical
applications.
Here,
we
review
literature
summarize
knowledge
on
microRNA
regulation
pathophysiology
critically
discuss
whether
what
extent
these
increasing
insights
can
exploited
development
microRNA-based
therapeutics
clinic.
Biomolecules,
Journal Year:
2021,
Volume and Issue:
11(5), P. 767 - 767
Published: May 20, 2021
The
potential
to
treat
neurodegenerative
diseases
(NDs)
of
the
major
bioactive
compound
green
tea,
epigallocatechin-3-gallate
(EGCG),
is
well
documented.
Numerous
findings
now
suggest
that
EGCG
targets
protein
misfolding
and
aggregation,
a
common
cause
pathological
mechanism
in
many
NDs.
Several
studies
have
shown
interacts
with
misfolded
proteins
such
as
amyloid
beta-peptide
(Aβ),
linked
Alzheimer’s
disease
(AD),
α-synuclein,
Parkinson’s
(PD).
To
date,
NDs
constitute
serious
public
health
problem,
causing
financial
burden
for
care
systems
worldwide.
Although
current
treatments
provide
symptomatic
relief,
they
do
not
stop
or
even
slow
progression
these
devastating
disorders.
Therefore,
there
an
urgent
need
develop
effective
drugs
incurable
ailments.
It
expected
targeting
can
serve
therapeutic
strategy
since
neurodegeneration.
In
this
context,
may
offer
great
opportunities
drug
discovery
review
critically
discusses
role
provides
updated
information
on
scientific
evidence
potentially
be
used
fatal
brain
Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
38(1)
Published: Feb. 15, 2023
Neurodegenerative
diseases
such
as
Alzheimer's
disease
(AD)
are
multifactorial
with
several
different
pathologic
mechanisms.
Therefore,
it
is
assumed
that
multitargeted-directed
ligands
(MTDLs)
which
interact
biological
targets
relevant
to
the
diseases,
might
offer
an
improved
therapeutic
alternative
than
using
traditional
"one-target,
one-molecule"
approach.
Herein,
we
describe
new
benzothiazole-based
derivatives
a
privileged
scaffold
for
histamine
H3
receptor
(H3R).
The
most
affine
compound,
3-(azepan-1-yl)propyloxy-linked
benzothiazole
derivative
4b,
displayed
Ki
value
of
0.012
μM.
multitargeting
potential
these
H3R
towards
AChE,
BuChE
and
MAO-B
enzymes
was
evaluated
yield
compound
3s
(pyrrolidin-1-yl-(6-((5-(pyrrolidin-1-yl)pentyl)oxy)benzo[d]thiazol-2-yl)methanone)
promising
MTDL
0.036
μM
at
IC50
values
6.7
µM,
2.35
1.6
µM
BuChE,
MAO-B,
respectively.
These
findings
suggest
can
be
lead
structure
developing
multi-targeting
anti-AD
agents.
Journal of Medicinal Chemistry,
Journal Year:
2021,
Volume and Issue:
64(3), P. 1392 - 1422
Published: Feb. 2, 2021
The
natural
β-carboline
alkaloids
display
similarities
with
neurotransmitters
that
can
be
favorably
exploited
to
design
bioactive
and
bioavailable
drugs
for
Alzheimer's
disease
(AD)
therapy.
Several
AD
targets
are
currently
intensively
being
investigated,
divided
in
different
hypotheses:
mainly
the
cholinergic,
amyloid
β
(Aβ),
Tau
hypotheses.
To
date,
only
symptomatic
treatments
available
involving
acetylcholinesterase
NMDA
inhibitors.
On
basis
of
plethoric
single-target
structure–activity
relationship
studies,
scaffold
was
identified
as
a
powerful
tool
fostering
activity
molecular
interactions
wide
range
AD-related
targets.
This
knowledge
undoubtedly
used
multitarget-directed
ligands,
highly
relevant
strategy
preferred
context
multifactorial
pathology
intricate
etiology
such
AD.
In
this
review,
we
first
individually
discuss
β-carbolines,
then
focus
on
multitarget
strategies
dedicated
deliberate
new
efficient
scaffolds.
