Drug Delivery,
Год журнала:
2021,
Номер
28(1), С. 580 - 593
Опубликована: Янв. 1, 2021
Alzheimer's
disease
(AD)
is
a
degenerative
of
the
central
nervous
system
characterized
by
progressive
cognitive
and
memory-related
impairment.
However,
current
therapeutic
treatments
have
not
proved
sufficiently
effective,
mainly
due
to
complicated
pathogenesis
disease.
In
this
study,
nano-formulation
graphene
oxide
(GO)
loaded
with
dauricine
(Dau)
was
investigated
in
terms
combined
anti-inflammatory
anti-oxidative
stress
effects
Dau
inhibition
misfolding
aggregation
amyloid-β
(Aβ)
protein
GO.
Both
vivo
vitro
models
were
induced
using
Aβ1-42,
formulation
administered
nasally
mice.
The
results
showed
that
GO
greatly
reduced
oxidative
through
increasing
superoxide
dismutase
levels
decreasing
reactive
oxygen
species
malondialdehyde
vitro;
it
also
alleviated
memory
deficits
brain
glial
cell
activation
mice
Aβ1-42-induced
AD.
This
could
protect
against
damage
apoptosis
both
AD
models;
therefore,
has
potential
be
an
effective
agent
for
rapid
treatment
Current Neuropharmacology,
Год журнала:
2020,
Номер
18(11), С. 1106 - 1125
Опубликована: Май 28, 2020
The
only
conclusive
way
to
diagnose
Alzheimer's
is
carry
out
brain
autopsy
of
the
patient's
tissue
and
ascertain
whether
subject
had
or
any
other
form
dementia.
However,
due
non-feasibility
such
methods,
conclude
conditions,
medical
practitioners
use
tests
that
examine
a
mental
ability.Accurate
diagnosis
at
an
early
stage
need
hour
for
initiation
therapy.
cause
most
cases
still
remains
unknown
except
where
genetic
distinctions
have
been
observed.
Thus,
standard
drug
regimen
ensues
in
every
patient,
irrespective
cause,
which
may
not
always
be
beneficial
halting
reversing
disease
progression.
To
provide
better
life
patients
by
suppressing
existing
symptoms,
diagnosis,
curative
therapy,
site-specific
delivery
drugs,
application
hyphenated
methods
like
artificial
intelligence
brought
into
main
field
therapeutics.In
this
review,
we
compiled
hypotheses
explain
disease,
highlighted
gene
immunotherapy,
peptidomimetics,
metal
chelators,
probiotics
quantum
dots
as
advancements
strategies
manage
Alzheimer's.Biomarkers,
brain-imaging,
theranostics,
along
with
intelligence,
are
understood
future
management
Alzheimer's.
Journal of Trace Elements in Medicine and Biology,
Год журнала:
2021,
Номер
67, С. 126779 - 126779
Опубликована: Май 15, 2021
Alzheimer's
disease
(AD)
is
the
most
prevalent
cause
of
cognitive
impairment
and
dementia
worldwide.
The
pathobiology
has
been
studied
in
form
several
hypotheses,
ranging
from
oxidative
stress,
amyloid-beta
(Aβ)
aggregation,
accumulation
tau
forming
neurofibrillary
tangles
(NFT)
through
metal
dysregulation
homeostasis,
dysfunction
cholinergic
system,
to
inflammatory
autophagic
mechanism.
However,
none
these
hypotheses
led
confirmed
diagnostics
or
approved
cure
for
disease.
This
review
aimed
as
a
basic
an
encyclopedic
short
course
into
metals
AD
discusses
advances
chelation
strategies
developments
adopted
treatment
Since
there
accumulating
evidence
role
both
biometal
dyshomeostasis
(iron
(Fe),
copper
(Cu),
zinc
(Zn))
metal-amyloid
interactions
that
lead
pathogenesis
AD,
this
focuses
on
unraveling
therapeutic
have
considered
disease,
aiming
sequester
free
protein-bound
ions
reducing
cerebral
burden.
Promising
compounds
possessing
chemically
modified
moieties
evolving
multi-target
ligands
used
anti-AD
drug
candidates
are
also
covered.
Several
multidirectional
multifaceted
studies
therapeutics
show
need
improved
synthesis,
screening,
analysis
be
able
effectively
present
chelating
drugs.
Most
limitations
their
physicochemical
properties;
some
enhance
redistribution
ions,
while
others
indirectly
activate
signaling
pathways
AD.
process
vivo
still
needs
established
design
potential
bi-functionally
well
inhibit
Aβ
aggregation
by
competing
with
metal-induced
damage
neurotoxicity
may
signal
bright
end
chelation-based
iScience,
Год журнала:
2020,
Номер
23(4), С. 101005 - 101005
Опубликована: Март 25, 2020
Multiple
lines
of
evidence
indicate
that
amyloid
beta
(Aβ)
peptide
is
responsible
for
the
pathological
devastation
caused
in
Alzheimer's
disease
(AD).
Aβ
aggregation
species
predominantly
contribute
to
multifaceted
toxicity
observed
neuronal
cells
including
generation
reactive
oxygen
(ROS),
mitochondrial
dysfunction,
interfering
with
synaptic
signaling,
and
activation
premature
apoptosis.
Herein,
we
report
a
natural
product
berberine-derived
(Ber-D)
multifunctional
inhibitor
ameliorate
cellulo
AD.
The
structural
attributes
polyphenolic
Ber-D
have
contributed
its
efficient
Cu
chelation
arresting
redox
cycle
prevent
ROS
rescue
biomacromolecules
from
oxidative
damage.
inhibits
metal-dependent
-independent
aggregation,
which
supported
by
silico
studies.
treatment
averts
dysfunction
corresponding
contributing
These
key
make
potential
therapeutic
candidate
Chemical Science,
Год журнала:
2022,
Номер
13(46), С. 13657 - 13689
Опубликована: Янв. 1, 2022
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
and
major
contributor
to
dementia
cases
worldwide.
AD
clinically
characterized
by
learning,
memory,
cognitive
deficits.
The
accumulation
of
extracellular
amyloid
β
(Aβ)
plaques
neurofibrillary
tangles
(NFTs)
tau
are
the
pathological
hallmarks
explored
as
targets
for
clinical
diagnosis
therapy.
pathology
poorly
understood
there
no
fully
approved
treatments.
Notwithstanding
gap,
decades
research
in
understanding
mechanisms
have
revealed
multifactorial
nature
AD.
As
result,
multipronged
holistic
approaches
pertinent
targeting
multiple
biomarkers
developing
effective
therapeutics.
In
this
perspective,
recent
developments
Aβ
targeted
diagnostic
therapeutic
tools
discussed.
Novel
indirect,
combination,
circulating
potential
highlighted.
We
underline
importance
multiplexing
multimodal
detection
generate
biomarker
fingerprints
reliable
strategy.
classical
therapeutics
aggregation
pathways
described
with
bottlenecks
Drug
discovery
efforts
multifaceted
toxicity
involving
protein
aggregation,
metal
toxicity,
oxidative
stress,
mitochondrial
damage,
neuroinflammation
Recent
focused
on
strategies
rationally
design
multifunctional
modulators
factors
presented
future
drug
development
discover
ACS Chemical Neuroscience,
Год журнала:
2018,
Номер
10(1), С. 588 - 598
Опубликована: Окт. 15, 2018
The
fibrillogenesis
of
amyloid-β
protein
(Aβ)
is
considered
a
crucial
factor
in
the
pathogenesis
Alzheimer's
disease
(AD).
Hence,
inhibiting
Aβ
regarded
as
primary
therapeutic
strategy
for
prevention
and
treatment
AD.
However,
development
effective
inhibitors
against
has
faced
significant
challenges.
Previous
studies
have
shown
that
pristine
single-walled
carbon
nanotubes
(SWNTs)
can
inhibit
some
amyloid
proteins.
poor
dispersibility
SWNTs
an
aqueous
environment
greatly
hinders
their
inhibitory
efficacy.
Here,
we
examined
activity
hydroxylated
(SWNT-OH)
on
aggregation
cytotoxicity
Aβ42
using
thioflavin
T
(ThT)
fluorescence,
atomic
force
microscopy
(AFM),
cellular
viability
assays,
molecular
dynamics
(MD)
simulations.
ThT
AFM
results
showed
SWNT-OH
inhibits
disaggregates
preformed
fibrils
dose-dependent
manner.
Furthermore,
ratio
hydroxyl
groups
effect
aggregation.
exerted
cytoprotective
effects
fibrillation-induced
cytotoxicity.
free-energy
decomposition
based
MD
simulations
revealed
nonpolar
interactions,
especially
van
der
Waals
forces,
contributed
most
free
energy
binding
SWNT-OH-Aβ
complex.
Two
regions
pentamer
were
identified
to
interact
with
SWNT-OH,
spanning
H13-Q15
V36-G38.
findings
presented
here
will
contribute
comprehensive
understanding
nanoparticles
fibrillogenesis,
which
critical
search
more
agents
counteract
amyloid-mediated
pathologies.
