Acta Neuropathologica Communications,
Год журнала:
2023,
Номер
11(1)
Опубликована: Ноя. 14, 2023
Abstract
Tau
seed
amplification
assays
(SAAs)
directly
measure
the
seeding
activity
of
tau
and
would
therefore
be
ideal
biomarkers
for
clinical
trials
targeting
seeding-competent
in
Alzheimer’s
disease
(AD).
However,
precise
relationship
between
measured
by
SAA
levels
pathological
forms
AD
brain
remains
unknown.
We
developed
a
new
based
on
full-length
0N3R
with
sensitivity
low
fg/ml
range
used
it
to
characterize
103
samples
from
three
independent
cohorts.
clearly
discriminated
control
samples.
Interestingly,
was
absent
Progressive
Supranuclear
Palsy
(PSP)
putamen,
suggesting
that
our
did
not
amplify
4R
aggregates
PSP
brain.
The
specificity
further
supported
analysis
matched
hippocampus
cerebellum
While
detected
Braak
stages
I-II,
no
present
is
devoid
inclusions.
Analysis
40
middle
frontal
gyrus
encompassing
all
showed
gradually
increased
stage.
This
presence
inclusions
robust
correlations
results
phosphorylated
tau212/214,
tau181,
aggregated
tau,
sarkosyl-insoluble
tau.
Strikingly,
we
already
at
stage
II-III,
can
detect
pathology
earlier
than
conventional
immunohistochemical
staining.
In
conclusion,
data
suggest
quantitative
human
provides
an
important
basis
development
accessible
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(2), С. 616 - 616
Опубликована: Янв. 6, 2022
Dementia
is
a
neurodegenerative
condition
that
considered
major
factor
contributing
to
cognitive
decline
reduces
independent
function.
Pathophysiological
pathways
are
not
well
defined
for
diseases
such
as
dementia;
however,
published
evidence
has
shown
the
role
of
numerous
inflammatory
processes
in
brain
toward
their
pathology.
Microglia
central
nervous
system
(CNS)
principal
components
brain’s
immune
defence
and
can
detect
harmful
or
external
pathogens.
When
stimulated,
cells
trigger
neuroinflammatory
responses
by
releasing
proinflammatory
chemokines,
cytokines,
reactive
oxygen
species,
nitrogen
species
order
preserve
cell’s
microenvironment.
These
markers
include
cytokines
IL-1,
IL-6,
TNFα
chemokines
CCR3
CCL2
CCR5.
Microglial
may
produce
prolonged
response
that,
some
circumstances,
indicated
promotion
diseases.
The
present
review
focused
on
involvement
microglial
cell
activation
throughout
conditions
link
between
dementia.
Biomolecules,
Год журнала:
2023,
Номер
13(2), С. 313 - 313
Опубликована: Фев. 7, 2023
The
deposition
of
amyloid-beta
(Aβ)
plaques
in
the
brain
is
one
primary
pathological
characteristics
Alzheimer’s
disease
(AD).
It
can
take
place
20–30
years
before
onset
clinical
symptoms.
imbalance
between
production
and
clearance
Aβ
major
causes
AD.
Enhancing
at
an
early
stage
attractive
preventive
therapeutic
strategy
Direct
inhibition
aggregation
using
small
molecules,
peptides,
monoclonal
antibody
drugs
has
not
yielded
satisfactory
efficacy
trials
for
decades.
Novel
approaches
are
required
to
understand
combat
deposition.
Neurological
dysfunction
a
complex
process
that
integrates
functions
different
types
cells
brain.
role
non-neurons
AD
been
fully
elucidated.
An
in-depth
understanding
interactions
neurons
contribute
elucidation
formation
identification
effective
drug
targets.
patient-derived
pluripotent
stem
(PSCs)
contain
complete
background
information
have
potential
differentiate
into
various
vitro,
which
may
bring
new
insight
treatment
Here,
we
systematically
review
latest
studies
on
clarify
roles
cell
among
microglia,
astroglia
response
plaques,
will
be
beneficial
explore
methods
reconstructing
models
inducible
PSCs
(iPSCs)
through
differentiation
techniques
validating
applications
plaques.
This
provide
most
promising
directions
finding
clues
preventing
delaying
development
Acta Pharmaceutica Sinica B,
Год журнала:
2023,
Номер
13(5), С. 2152 - 2175
Опубликована: Янв. 19, 2023
We
describe
the
development
of
quinolylnitrones
(QNs)
as
multifunctional
ligands
inhibiting
cholinesterases
(ChEs:
acetylcholinesterase
and
butyrylcholinesterase-hBChE)
monoamine
oxidases
(hMAO-A/B)
for
therapy
neurodegenerative
diseases.
identified
QN
19,
a
simple,
low
molecular
weight
nitrone,
that
is
readily
synthesized
from
commercially
available
8-hydroxyquinoline-2-carbaldehyde.
Quinolylnitrone
19
has
no
typical
pharmacophoric
element
to
suggest
ChE
or
MAO
inhibition,
yet
unexpectedly
showed
potent
inhibition
hBChE
(IC50
=
1.06
±
0.31
nmol/L)
hMAO-B
4.46
0.18
μmol/L).
The
crystal
structures
with
provided
structural
basis
binding,
which
was
further
studied
by
enzyme
kinetics.
Compound
acted
free
radical
scavenger
biometal
chelator,
crossed
blood-brain
barrier,
not
cytotoxic,
neuroprotective
properties
in
6-hydroxydopamine
cell
model
Parkinson's
disease.
In
addition,
vivo
studies
anti-amnesic
effect
scopolamine-induced
mouse
AD
without
adverse
effects
on
motoric
function
coordination.
Importantly,
chronic
treatment
double
transgenic
APPswe-PS1δE9
mice
reduced
amyloid
plaque
load
hippocampus
cortex
female
mice,
underscoring
disease-modifying
19.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 4062 - 4062
Опубликована: Апрель 5, 2024
Recently,
studies
have
reported
a
correlation
that
individuals
with
diabetes
show
an
increased
risk
of
developing
Alzheimer’s
disease
(AD).
Mulberry
leaves,
serving
as
both
traditional
medicinal
herb
and
food
source,
exhibit
significant
hypoglycemic
antioxidative
properties.
The
flavonoid
compounds
in
mulberry
leaf
offer
therapeutic
effects
for
relieving
diabetic
symptoms
providing
neuroprotection.
However,
the
mechanisms
this
effect
not
been
fully
elucidated.
This
investigation
aimed
to
investigate
combined
specific
flavonoids
(kaempferol,
quercetin,
rhamnocitrin,
tetramethoxyluteolin,
norartocarpetin)
on
type
2
mellitus
(T2DM)
AD.
Additionally,
role
gut
microbiota
these
two
diseases’
treatment
was
studied.
Using
network
pharmacology,
we
investigated
potential
microbiota,
combating
AD
T2DM.
In
addition,
identified
protein
tyrosine
phosphatase
1B
(PTP1B)
key
target
kaempferol
diseases.
Molecular
docking
molecular
dynamics
simulations
showed
has
inhibit
PTP1B
indirect
AD,
which
proven
by
measuring
IC50
(279.23
μM).
cell
experiment
also
confirmed
dose-dependent
phosphorylation
total
cellular
HepG2
cells.
research
supports
concept
food–medicine
homology
broadens
range
medical
treatments
highlighting
prospect
integrating
herbal
remedies
modern
research.
