Journal of Medicinal Chemistry,
Journal Year:
2015,
Volume and Issue:
58(17), P. 6972 - 6983
Published: Aug. 11, 2015
Alzheimer's
disease
(AD)
is
pathologically
characterized
by
the
accumulation
of
β-amyloid
(Aβ)
deposits
in
parenchymal
and
cortical
brain.
In
this
work,
we
designed,
synthesized,
evaluated
a
series
near-infrared
(NIR)
probes
with
electron
donor–acceptor
end
groups
interacting
through
π-conjugated
system
for
detection
Aβ
Among
these
probes,
3b
3c
had
excellent
fluorescent
properties
(emission
maxima
>
650
nm
high
quantum
yields)
displayed
sensitivity
affinities
to
aggregates
(3b,
Kd
=
8.8
nM;
3c,
1.9
nM).
Both
could
readily
penetrate
blood–brain
barrier
initial
brain
uptake
fast
moderate
washout
from
vivo
NIR
imaging
revealed
that
efficiently
differentiate
transgenic
wild-type
mice.
summary,
our
research
provides
new
hints
developing
smarter
more
activatable
targeting
Aβ.
Nature Communications,
Journal Year:
2015,
Volume and Issue:
6(1)
Published: Jan. 29, 2015
In
Alzheimer’s
disease
(AD),
β-amyloid
(Aβ)
plaques
are
tightly
enveloped
by
microglia
processes,
but
the
significance
of
this
phenomenon
is
unknown.
Here
we
show
that
constitute
a
barrier
with
profound
impact
on
plaque
composition
and
toxicity.
Using
high-resolution
confocal
in
vivo
two-photon
imaging
AD
mouse
models,
demonstrate
prevents
outward
expansion
leads
to
compact
microregions
low
Aβ42
affinity.
Areas
uncovered
less
have
high
affinity,
leading
formation
protofibrillar
hotspots
associated
more
severe
axonal
dystrophy.
ageing,
coverage
reduced
enlarged
neuritic
CX3CR1
gene
deletion
or
anti-Aβ
immunotherapy
causes
Failure
accumulation
neurotoxic
Aβ
may
novel
therapeutic
clinical
targets
for
AD.
authors
used
vivotwo-photon
models
revealed
seems
prevent
β-amyloid.
Journal of the American Chemical Society,
Journal Year:
2019,
Volume and Issue:
141(7), P. 3171 - 3177
Published: Jan. 11, 2019
High-fidelity
mapping
of
amyloid-β
(Aβ)
plaques
is
critical
for
the
early
detection
Alzheimer's
disease.
However,
in
vivo
probing
Aβ
by
commercially
available
thioflavin
derivatives
(ThT
or
ThS)
has
proven
to
be
extremely
limited,
as
evident
restriction
enrichment
quenching
effect,
low
signal-to-noise
(S/N)
ratio,
and
poor
blood–brain
barrier
(BBB)
penetrability.
Herein,
we
demonstrate
a
rational
design
strategy
near-infrared
(NIR)
aggregation-induced
emission
(AIE)-active
probes
plaques,
through
introducing
lipophilic
π-conjugated
thiophene-bridge
extension
NIR
wavelength
range
with
enhancement
BBB
penetrability,
tuning
substituted
position
sulfonate
group
guaranteeing
specific
hydrophilicity
maintain
fluorescence-off
state
before
binding
deposition.
Probe
QM-FN-SO3
settled
well
AIE
dilemma
between
requirement
longer
aggregation
behavior
from
water
protein
fibrillogenesis,
thus
making
breakthrough
high-fidelity
feedback
on
remarkable
affinity,
serving
an
efficient
alternative
commercial
probe
ThT
ThS.
Chemical Reviews,
Journal Year:
2019,
Volume and Issue:
119(23), P. 11819 - 11856
Published: Nov. 1, 2019
Amyloids
are
a
broad
class
of
proteins
and
peptides
that
can
misfold
assemble
into
long
unbranched
fibrils
with
cross-β
conformation.
These
misfolding
aggregation
events
associated
the
onset
variety
human
diseases,
among
them,
Alzheimer's
disease,
Parkinson's
Huntington
disease.
Our
understanding
amyloids
has
been
greatly
supported
by
fluorescent
molecular
probes,
such
as
thioflavin-T,
which
shows
an
increase
in
fluorescence
emission
upon
binding
to
fibrillar
aggregates.
Since
first
application
thioflavin-T
amyloid
studies
nearly
30
years
ago,
many
probes
have
emerged
exhibiting
responses
amyloids,
intensity
changes,
shifts
maxima,
variations
lifetimes,
others.
shed
light
on
topics
including
kinetics
aggregation,
effectiveness
inhibitors,
elucidation
sites
structures,
staining
aggregates
vitro,
ex
vivo,
vivo.
In
this
Review,
we
discuss
design,
properties,
photoactive
used
study
well
challenges
faced
current
techniques,
novel
approaches
emerging
address
these
challenges.
Proceedings of the National Academy of Sciences,
Journal Year:
2015,
Volume and Issue:
112(31), P. 9734 - 9739
Published: July 21, 2015
Near-infrared
fluorescence
(NIRF)
molecular
imaging
has
been
widely
applied
to
monitoring
therapy
of
cancer
and
other
diseases
in
preclinical
studies;
however,
this
technology
not
successfully
for
Alzheimer's
disease
(AD).
Although
several
NIRF
probes
detecting
amyloid
beta
(Aβ)
species
AD
have
reported,
none
these
used
monitor
changes
Aβs
during
therapy.
In
article,
we
demonstrated
that
CRANAD-3,
a
curcumin
analog,
is
capable
both
soluble
insoluble
Aβ
species.
vivo
showed
the
signal
CRANAD-3
from
4-mo-old
transgenic
(APP/PS1)
mice
was
2.29-fold
higher
than
age-matched
wild-type
mice,
indicating
early
pathology.
To
verify
feasibility
therapy,
first
fast
Aβ-lowering
drug
LY2811376,
well-characterized
beta-amyloid
cleaving
enzyme-1
inhibitor,
treat
APP/PS1
mice.
Imaging
data
suggested
could
decrease
after
treatment.
validate
capacity
further,
it
therapeutic
effect
CRANAD-17,
analog
inhibition
cross-linking.
The
indicated
CRANAD-17-treated
group
significantly
lower
control
group,
result
correlated
with
ELISA
analysis
brain
extraction
plaque
counting.
It
time,
our
knowledge,
believe
potential
high
impact
on
development.
Neural Regeneration Research,
Journal Year:
2018,
Volume and Issue:
13(4), P. 742 - 742
Published: Jan. 1, 2018
This
review
summarizes
and
describes
the
use
of
curcumin
in
diagnosis,
prevention,
treatment
Alzheimer's
disease.
For
diagnosis
disease,
amyloid-β
highly
phosphorylated
tau
protein
are
major
biomarkers.
Curcumin
was
developed
as
an
early
diagnostic
probe
based
on
its
natural
fluorescence
high
binding
affinity
to
amyloid-β.
Because
multi-target
effects,
has
protective
preventive
effects
many
chronic
diseases
such
cerebrovascular
hypertension,
hyperlipidemia.
prevention
been
shown
effectively
maintain
normal
structure
function
cerebral
vessels,
mitochondria,
synapses,
reduce
risk
factors
for
a
variety
diseases,
decrease
The
effect
disease
involves
multiple
signaling
pathways:
anti-amyloid
metal
iron
chelating
properties,
antioxidation
anti-inflammatory
activities.
Indeed,
there
is
scientific
basis
rational
application
Advanced Materials,
Journal Year:
2020,
Volume and Issue:
32(51)
Published: Sept. 9, 2020
Abstract
Neurodegenerative
diseases
are
debilitating
disorders
that
feature
progressive
and
selective
loss
of
function
or
structure
anatomically
physiologically
associated
neuronal
systems.
Both
chronic
acute
neurodegenerative
with
high
morbidity
mortality
along
the
death
neurons
in
different
areas
brain;
moreover,
there
few
no
effective
curative
therapy
options
for
treating
these
disorders.
There
is
an
urgent
need
to
diagnose
disease
as
early
possible,
distinguish
between
overlapping
symptoms
will
help
decide
best
clinical
treatment.
Recently,
research,
fluorescent‐probe‐mediated
biomarker
visualization
techniques
have
been
gaining
increasing
attention
diagnosis
diseases.
A
survey
fluorescent
probes
sensing
imaging
biomarkers
provided.
These
categorized
based
on
potential
various
diseases,
their
advantages
disadvantages
discussed.
Guides
develop
new
strategies,
recognition
mechanisms,
well
ideal
features
further
improve
fluorescence
also
explored.
Journal of Clinical Medicine,
Journal Year:
2020,
Volume and Issue:
9(2), P. 430 - 430
Published: Feb. 5, 2020
The
brain
is
the
body's
control
center,
so
when
a
disease
affects
it,
outcomes
are
devastating.
Alzheimer's
and
Parkinson's
disease,
multiple
sclerosis
diseases
that
cause
large
number
of
human
deaths
worldwide.
Curcumin
has
demonstrated
beneficial
effects
on
health
through
several
mechanisms
such
as
antioxidant,
amyloid
β-binding,
anti-inflammatory,
tau
inhibition,
metal
chelation,
neurogenesis
activity,
synaptogenesis
promotion.
therapeutic
limitation
curcumin
its
bioavailability,
to
address
this
problem,
new
nanoformulations
being
developed.
present
review
aims
summarize
general
bioactivity
in
neurological
disorders,
how
functional
molecules
extracted,
different
types
available.
Chemical Communications,
Journal Year:
2019,
Volume and Issue:
56(7), P. 1050 - 1053
Published: Dec. 15, 2019
It
has
been
speculated
that
both
the
intracellular
viscosity
and
H2O2
level
in
Alzheimer's
disease
(AD)
brains
are
higher
than
healthy
brains,
but
direct
evidence
from
living
beings
is
scarce.
Herein,
we
report
a
NIR
emissive
fluorescent
probe
with
large
Stokes
shift
for
associated
detection
of
mitochondrial
live
rat
AD
first
time.
