International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
24(1), С. 241 - 241
Опубликована: Дек. 23, 2022
The
study
of
diseases
the
central
nervous
system
(CNS)
at
molecular
level
is
challenging
because
complexity
neural
circuits
and
huge
number
specialized
cell
types.
Moreover,
genomic
association
studies
have
revealed
complex
genetic
architecture
schizophrenia
other
genetically
determined
mental
disorders.
Investigating
such
to
decipher
basis
CNS
pathologies
requires
use
high-throughput
models
as
cells
their
derivatives.
time
coming
for
technologies
based
on
CRISPR
(Clustered
Regularly
Interspaced
Short
Palindromic
Repeat)/Cas
systems
manipulate
multiple
targets.
CRISPR/Cas
provide
desired
complexity,
versatility,
flexibility
create
novel
tools
capable
both
altering
DNA
sequence
affecting
its
function
higher
levels
information
flow.
make
it
possible
find
investigate
intricate
relationship
between
genotype
phenotype
neuronal
cells.
purpose
this
review
discuss
innovative
CRISPR-based
approaches
studying
mechanisms
using
cellular
models.
Biological Trace Element Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 26, 2024
Abstract
The
SH-SY5Y
cell
line
is
widely
used
in
neurotoxicity
studies.
However,
the
effects
of
inducing
differentiation
on
cytotoxic
heavy
metals
are
unclear.
Therefore,
we
investigated
mercuric
chloride
(HgCl
2
),
cadmium
(CdCl
arsenic
trioxide
(As
O
3
and
methylmercury
(MeHg)
cells
differentiated
presence
insulin-like
growth
factor-I
(IGF-I)
or
all-trans
retinoic
acid
(ATRA).
Neurite
outgrowth
with
distinct
changes
neuronal
marker
expression,
phenotype,
cycle
was
induced
by
IGF-I
treatment
for
1
day
ATRA
up
to
7
days.
HgCl
decreased
at
lower
concentrations
increased
higher
both
IGF-I-
ATRA-differentiated
compared
those
undifferentiated
cells.
Differentiation
IGF-I,
but
not
ATRA,
CdCl
.
Decreased
As
MeHg
were
observed
IGF-I-differentiated
cells,
whereas
Changes
even
after
exposure
Our
results
demonstrate
that
induces
different
cellular
characteristics,
resulting
diverse
sensitivity
metals,
which
depend
only
agents
time
also
metal
species
concentration.
Glioblastoma
multiforme
(GBM)
is
highly
aggressive
and
difficult
to
treat,
necessitating
the
development
of
new
therapies.
Photoactivated
chemotherapy
(PACT)
has
emerged
as
a
promising
method,
where
biologically
active
compounds
are
“caged”
into
inactive
prodrugs,
re-activated
by
visible
light
irradiation
at
tumor
site,
potentially
offering
more
patient-friendly
treatments
without
compromising
antitumor
efficacy.
In
this
study,
we
investigated
activity
series
ruthenium-based
PACT
[1](PF6)2-[3](PF6)2
in
U-87MG
glioblastoma
cells,
common
vitro
model
for
glioblastoma,
safety
these
SH-SY5Y
which
recognized
healthy
neurons.
The
action
was
compared
that
Donepezil,
known
acetylcholinesterase
inhibitor
used
treatment
brain
disorders.
Promising
light-activated
anticancer
observed
cells
[3](PF6)2
while
two
other
were
inactive([1](PF6)2)
or
non-activated
([2](PF6)2).
non-cancerous
complexes
surprisingly
enhanced
cell
proliferation
manner
similar
Donepezil.
While
significantly
higher
amounts
Ru
found
upon
green
irradiation,
particular
[3](PF6)2,
effect
independent
from
ruthenium
cellular
uptake.
Given
importance
Ca2+
levels
normal
function
neurons,
also
examined
accumulation
with
light.
Increased
uptake
treated
inactivated
[1](PF6)2
,
[2](PF6)2
only.
Upon
intracellular
content
not
changed
dark
but
it
increased
activation,
observable
sign
death.
structure-dependent
on
homeostasis
suggested
docking
studies
NMDA,
serotonin,
AMPA
receptors,
all
act
calcium
levels.
Docking
revealed
interacts
NMDA
receptor,
might
be
responsible
activation
cells.
Overall,
although
phototoxic
combination
prodrug
survival
neuronal-like
levels,
probably
via
interaction
receptor.
These
findings
highlight
potential
prodrugs
treating
maintaining
viability
nearby,
neuronal
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Ноя. 25, 2024
Neurodegenerative
diseases
(NDDs)
present
significant
challenges
due
to
limited
treatment
options,
ethical
concerns
surrounding
traditional
animal
models,
and
the
time-consuming
costly
process
of
using
human-induced
pluripotent
stem
cells
(iPSCs).
We
addressed
these
issues
by
developing
a
3D
culture
protocol
for
differentiating
SH-SY5Y
into
glutamatergic
neurons,
enhancing
physiological
relevance
with
microarray
plate.
Our
optimized
serum
concentration
incorporated
retinoic
acid
(RA)
improve
differentiation.
analyzed
proportions
N-type
S-type
cells,
observing
that
RA
in
maturation
stage
not
only
reduced
cell
proliferation
but
also
enhanced
expression
MAP2
VGLUT1,
indicating
effective
neuronal
approach
demonstrates
strong
neuron
phenotypes
neural
spheroids,
offering
promising
tool
high-throughput
NDD
modeling
advancing
drug
discovery
therapeutic
development.
This
method
overcomes
limitations
associated
conventional
2D
cultures
providing
more
platform
research.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
24(1), С. 241 - 241
Опубликована: Дек. 23, 2022
The
study
of
diseases
the
central
nervous
system
(CNS)
at
molecular
level
is
challenging
because
complexity
neural
circuits
and
huge
number
specialized
cell
types.
Moreover,
genomic
association
studies
have
revealed
complex
genetic
architecture
schizophrenia
other
genetically
determined
mental
disorders.
Investigating
such
to
decipher
basis
CNS
pathologies
requires
use
high-throughput
models
as
cells
their
derivatives.
time
coming
for
technologies
based
on
CRISPR
(Clustered
Regularly
Interspaced
Short
Palindromic
Repeat)/Cas
systems
manipulate
multiple
targets.
CRISPR/Cas
provide
desired
complexity,
versatility,
flexibility
create
novel
tools
capable
both
altering
DNA
sequence
affecting
its
function
higher
levels
information
flow.
make
it
possible
find
investigate
intricate
relationship
between
genotype
phenotype
neuronal
cells.
purpose
this
review
discuss
innovative
CRISPR-based
approaches
studying
mechanisms
using
cellular
models.
