Advanced Materials,
Год журнала:
2024,
Номер
36(19)
Опубликована: Фев. 23, 2024
Abstract
The
accumulation
of
hyperphosphorylated
tau
protein
aggregates
is
a
key
pathogenic
event
in
Alzheimer's
disease
(AD)
and
induces
mitochondrial
dysfunction
reactive
oxygen
species
overproduction.
However,
the
treatment
AD
remains
challenging
owning
to
hindrance
caused
by
blood–brain
barrier
(BBB)
complex
pathology
AD.
Nasal
delivery
represents
an
effective
means
circumventing
BBB
delivering
drugs
brain.
In
this
study,
black
phosphorus
(BP)
used
as
drug
carrier,
well
antioxidant,
loaded
with
aggregation
inhibitor,
methylene
blue
(MB),
obtain
BP‐MB.
For
intranasal
(IN)
delivery,
thermosensitive
hydrogel
fabricated
cross‐linking
carboxymethyl
chitosan
aldehyde
Pluronic
F127
(F127‐CHO)
micelles.
BP‐MB
nanocomposite
incorporated
into
BP‐MB@Gel.
BP‐MB@Gel
could
be
injected
intranasally,
providing
high
nasal
mucosal
retention
controlled
release.
After
IN
administration,
continuously
released
delivered
brain,
exerting
synergistic
therapeutic
effects
suppressing
neuropathology,
restoring
function,
alleviating
neuroinflammation,
thus
inducing
cognitive
improvements
mouse
models
These
findings
highlight
potential
strategy
for
brain‐targeted
management
pathologies
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(9), С. 5023 - 5023
Опубликована: Апрель 30, 2022
Positron
emission
tomography
(PET)
uses
radioactive
tracers
and
enables
the
functional
imaging
of
several
metabolic
processes,
blood
flow
measurements,
regional
chemical
composition,
and/or
absorption.
Depending
on
targeted
processes
within
living
organism,
different
are
used
for
various
medical
conditions,
such
as
cancer,
particular
brain
pathologies,
cardiac
events,
bone
lesions,
where
most
commonly
radiolabeled
with
18F
(e.g.,
[
Journal of Neuroinflammation,
Год журнала:
2021,
Номер
18(1)
Опубликована: Июнь 11, 2021
Abstract
Background
Tau
pathology
is
a
hallmark
of
Alzheimer’s
disease
(AD)
and
other
tauopathies.
During
progression,
abnormally
phosphorylated
forms
tau
aggregate
accumulate
into
neurofibrillary
tangles,
leading
to
synapse
loss,
neuroinflammation,
neurodegeneration.
Thus,
targeting
expected
be
promising
strategy
for
AD
treatment.
Methods
The
effect
rutin
on
aggregation
was
detected
by
thioflavin
T
fluorescence
transmission
electron
microscope
imaging.
oligomer-induced
cytotoxicity
assessed
MTT
assay.
oligomer-mediated
the
production
IL-1β
TNF-α
in
vitro
measured
ELISA.
uptake
extracellular
microglia
determined
immunocytochemistry.
Six-month-old
male
Tau-P301S
mice
were
treated
with
or
vehicle
oral
administration
daily
30
days.
cognitive
performance
using
Morris
water
maze
test,
Y-maze
novel
object
recognition
test.
levels
pathological
tau,
gliosis,
NF-kB
activation,
proinflammatory
cytokines
such
as
TNF-α,
synaptic
proteins
including
synaptophysin
PSD95
brains
evaluated
immunolabeling,
immunoblotting,
Results
We
showed
that
rutin,
natural
flavonoid
glycoside,
inhibited
cytotoxicity,
lowered
cytokines,
protected
neuronal
morphology
from
toxic
oligomers,
promoted
microglial
oligomers
vitro.
When
applied
mouse
model
tauopathy,
reduced
levels,
regulated
hyperphosphorylation
increasing
PP2A
level,
suppressed
gliosis
neuroinflammation
downregulating
pathway,
prevented
engulfment,
rescued
loss
brains,
resulting
significant
improvement
cognition.
Conclusion
In
combination
previously
reported
therapeutic
effects
Aβ
pathology,
drug
candidate
treatment
based
its
combinatorial
Aβ.
Oxidative Medicine and Cellular Longevity,
Год журнала:
2018,
Номер
2018(1)
Опубликована: Янв. 1, 2018
Alzheimer’s
and
Parkinson’s
diseases
are
considered
the
most
common
neurodegenerative
disorders,
representing
a
major
focus
of
neuroscience
research
to
understanding
cellular
alterations
pathophysiological
mechanisms
involved.
Several
natural
products,
including
flavonoids,
able
cross
blood‐brain
barrier
known
for
their
central
nervous
system‐related
activity.
Therefore,
studies
being
conducted
with
these
chemical
constituents
analyze
activities
in
slowing
down
progression
diseases.
The
present
systematic
review
summarizes
pharmacological
effects
flavonoids
animal
models
A
PRISMA
model
was
utilized
this
search.
following
databases:
PubMed,
Web
Science,
BIREME,
Science
Direct.
Based
on
inclusion
criteria,
31
articles
were
selected
discussed
review.
listed
revealed
that
main
targets
action
disease
therapy
reduction
reactive
oxygen
species
amyloid
beta‐protein
production,
while
oxidative
potential
activation
neuronal
death.
Results
showed
variety
is
studied
can
be
promising
development
new
drugs
treat
Moreover,
it
possible
verify
there
lack
translational
clinical
evidence
compounds.
Journal of Neuroinflammation,
Год журнала:
2023,
Номер
20(1)
Опубликована: Июль 14, 2023
Abstract
Alzheimer’s
Disease
(AD)
contributes
to
most
cases
of
dementia.
Its
prominent
neuropathological
features
are
the
extracellular
neuritic
plaques
and
intercellular
neurofibrillary
tangles
composed
aggregated
β-amyloid
(Aβ)
hyperphosphorylated
tau
protein,
respectively.
In
past
few
decades,
disease-modifying
therapy
targeting
Aβ
has
been
focus
AD
drug
development.
Even
though
it
is
encouraging
that
two
these
drugs
have
recently
received
accelerated
US
Food
Drug
Administration
approval
for
treatment,
their
efficacy
or
long-term
safety
controversial.
Tau
increasing
attention
as
a
potential
therapeutic
target,
since
evidence
indicates
pathology
more
associated
with
cognitive
dysfunction.
Moreover,
inflammation,
especially
neuroinflammation,
accompanies
pathological
processes
also
linked
deficits.
Accumulating
inflammation
complex
tight
interplay
pathology.
Here,
we
review
recent
on
interaction
between
pathology,
focusing
post-translational
modification
dissemination,
neuroinflammatory
responses,
including
glial
cell
activation
inflammatory
signaling
pathways.
Then,
summarize
latest
clinical
trials
neuroinflammation.
Sustained
increased
responses
in
cells
neurons
pivotal
cellular
drivers
regulators
exacerbation
which
further
its
worsening
by
aggravating
responses.
Unraveling
precise
mechanisms
underlying
relationship
neuroinflammation
will
provide
new
insights
into
discovery
translation
targets
other
tau-related
diseases
(tauopathies).
Targeting
multiple
pathologies
precision
strategies
be
crucial
direction
developing
tauopathies.
Molecular Neurodegeneration,
Год журнала:
2019,
Номер
14(1)
Опубликована: Фев. 27, 2019
Alzheimer's
disease
is
characterized
by
two
main
neuropathological
hallmarks:
extracellular
plaques
of
amyloid-β
(Aβ)
protein
and
intracellular
aggregates
tau
protein.
Although
normally
a
soluble
monomer
that
bind
microtubules,
in
it
forms
insoluble,
hyperphosphorylated
the
cell
body.
Aside
from
its
role
AD,
also
involved
several
other
neurodegenerative
disorders
collectively
called
tauopathies,
such
as
progressive
supranuclear
palsy
(PSP),
corticobasal
degeneration
(CBD),
some
frontotemporal
dementia,
argyrophilic
grain
(AGD).
The
prion
hypothesis
suggests
after
an
initial
trigger
event,
misfolded
are
released
into
space,
where
they
spread
through
different
brain
regions,
enter
cells,
seeding
previously
normal
forms.
Thus
understanding
mechanisms
regulating
clearance
CNS
important.
discovery
true
lymphatic
system
dura
potential
mediating
Aβ
pathology
prompted
us
to
investigate
clearance.To
study
brain,
we
conjugated
monomeric
human
with
near-infrared
dye
cypate,
injected
this
labeled
parenchyma
both
wild-type
K14-VEGFR3-Ig
transgenic
mice,
which
lack
functional
system.
Following
injection
performed
longitudinal
imaging
using
fluorescence
molecular
tomography
(FMT)
quantified
calculate
brain.
To
complement
this,
measured
periphery
measuring
plasma
groups
mice.Our
results
show
significantly
higher
amount
retained
brains
vs.
wild
type
mice
at
48
72
h
post-injection
subsequent
delayed.
We
found
reference
tracer
serum
albumin
(HSA)
was
delayed
mice.The
dural
appears
play
important
tau,
since
impaired
absence
lymphatics.
Based
on
our
baseline
characterization
clearance,
future
studies
warranted
look
interaction
between
efficiency
function.
Frontiers in Cellular Neuroscience,
Год журнала:
2022,
Номер
15
Опубликована: Янв. 21, 2022
Neuroinflammation
plays
a
pivotal
role
in
Alzheimer's
disease
(AD)
and
Parkinson's
(PD),
the
leading
causes
of
dementia.
These
neurological
disorders
are
characterized
by
accumulation
misfolded
proteins
such
as
amyloid-ß
(Aß),
tau
protein
α-synuclein,
contributing
to
mitochondrial
fragmentation,
oxidative
stress,
neuroinflammation.
Misfolded
activate
microglia,
which
induces
neuroinflammation,
expression
pro-inflammatory
cytokines
subsequently
facilitates
synaptic
damage
neuronal
loss.
So
far,
all
proposed
drugs
were
based
on
inhibition
aggregation
failed
clinical
trials.
Therefore,
treatment
options
dementia
still
challenging
issue.
Thus,
it
is
worthwhile
study
alternative
therapeutic
strategies.
In
this
context,
there
increasing
data
transcription
factor
NF-
E2
p45-related
2
(Nrf2)
redox
homeostasis
anti-inflammatory
functions
neurodegenerative
disorders.
Interestingly,
Nrf2
signaling
pathway
has
shown
upregulation
antioxidant
genes,
microglia-mediated
inflammation,
improved
function
diseases,
suggesting
activation
could
be
novel
approach
target
pathogenesis.
The
present
review
will
examine
correlation
between
with
neuroinflammation
AD
PD.