Abstract
Alzheimer’s
disease
(AD)
is
one
of
the
most
prevalent
neurodegenerative
diseases,
yet
current
therapeutic
treatments
are
inadequate
due
to
a
complex
pathogenesis.
The
plant
polyphenol
apigenin
has
been
shown
have
anti-inflammatory
and
neuroprotective
properties
in
number
cell
animal
models;
however
comprehensive
assessment
not
performed
human
model
AD.
Here
we
used
induced
pluripotent
stem
(iPSC)
familial
sporadic
AD,
addition
healthy
controls,
assess
activity
apigenin.
iPSC-derived
AD
neurons
demonstrated
hyper-excitable
calcium
signalling
phenotype,
elevated
levels
nitrite,
increased
cytotoxicity
apoptosis,
reduced
neurite
length
susceptibility
inflammatory
stress
challenge
from
activated
murine
microglia,
comparison
control
neurons.
We
identified
that
potent
with
ability
protect
neurites
viability
by
promoting
global
down-regulation
cytokine
nitric
oxide
(NO)
release
cells.
In
addition,
show
able
via
multiple
means
reducing
frequency
spontaneous
Ca
2+
signals
significantly
caspase-3/7
mediated
apoptosis.
These
data
demonstrate
broad
action
against
pathogenesis
model.
Antioxidants,
Год журнала:
2020,
Номер
9(8), С. 647 - 647
Опубликована: Июль 22, 2020
Oxidative
stress
develops
as
a
response
to
injury
and
reflects
breach
in
the
cell’s
antioxidant
capacity.
Therefore,
fine-tuning
of
reactive
oxygen
species
(ROS)
generation
is
crucial
for
preserving
homeostasis.
Mitochondria
are
major
source
an
immediate
target
ROS.
Under
different
stimuli,
including
oxidative
impaired
quality
control,
mitochondrial
constituents
(e.g.,
DNA,
mtDNA)
displaced
toward
intra-
or
extracellular
compartments.
However,
mechanisms
responsible
mtDNA
unloading
remain
largely
unclear.
While
shuttling
freely
within
cell,
can
be
delivered
into
compartment
via
either
extrusion
entire
nucleoids
release
vesicles.
Once
discarded,
may
act
damage-associated
molecular
pattern
(DAMP)
trigger
innate
immune
inflammatory
by
binding
danger-signal
receptors.
Neuroinflammation
associated
with
large
array
neurological
disorders
which
DAMPs
could
represent
common
thread
supporting
disease
progression.
The
exploration
non-canonical
pathways
involved
control
neurodegeneration
unveil
novel
targets
development
therapeutic
agents.
Here,
we
discuss
these
processes
setting
two
neurodegenerative
diseases
(Alzheimer’s
Parkinson’s
disease)
Down
syndrome,
most
frequent
progeroid
syndrome.
Abstract
Alzheimer’s
disease
(AD)
is
one
of
the
most
prevalent
neurodegenerative
diseases,
yet
current
therapeutic
treatments
are
inadequate
due
to
a
complex
pathogenesis.
The
plant
polyphenol
apigenin
has
been
shown
have
anti-inflammatory
and
neuroprotective
properties
in
number
cell
animal
models;
however
comprehensive
assessment
not
performed
human
model
AD.
Here
we
used
induced
pluripotent
stem
(iPSC)
familial
sporadic
AD,
addition
healthy
controls,
assess
activity
apigenin.
iPSC-derived
AD
neurons
demonstrated
hyper-excitable
calcium
signalling
phenotype,
elevated
levels
nitrite,
increased
cytotoxicity
apoptosis,
reduced
neurite
length
susceptibility
inflammatory
stress
challenge
from
activated
murine
microglia,
comparison
control
neurons.
We
identified
that
potent
with
ability
protect
neurites
viability
by
promoting
global
down-regulation
cytokine
nitric
oxide
(NO)
release
cells.
In
addition,
show
able
via
multiple
means
reducing
frequency
spontaneous
Ca
2+
signals
significantly
caspase-3/7
mediated
apoptosis.
These
data
demonstrate
broad
action
against
pathogenesis
model.
