To activate a G protein-coupled receptor permanently with cell surface photodynamic action in the gastrointestinal tract
World Journal of Gastroenterology,
Journal Year:
2025,
Volume and Issue:
31(12)
Published: March 26, 2025
Different
from
reversible
agonist-stimulated
receptor
activation,
singlet
oxygen
oxidation
activates
permanently
G
protein-coupled
(GPCR)
cholecystokinin
1
(CCK1R)
in
type
II
photodynamic
action,
with
soluble
photosensitizer
dyes
(sulphonated
aluminum
phthalocyanine,
λmax
675
nm)
or
genetically
encoded
protein
photosensitizers
(KillerRed
585
nm;
mini
generator
450
nm),
together
a
pulse
of
light
(37
mW/cm2,
1-2
minutes).
Three
lines
evidence
shed
on
the
mechanism
GPCR
activated
by
(GPCR-ABSO):
(1)
CCK1R
is
quantitatively
converted
dimer
to
monomer;
(2)
Transmembrane
domain
3,
pharmacophore
for
permanent
can
be
transplanted
non-susceptible
M3
acetylcholine
receptor;
and
(3)
Larger
size
disordered
region
intracellular
loop
3
correlates
higher
sensitivity
activation.
GPCR-ABSO
will
add
arsenal
engineered
designer
such
as
receptors
solely
synthetic
ligands
exclusively
drugs,
but
show
some
clear
advantages:
Enhanced
selectivity
(double
localized
illumination),
long-lasting
activation
no
need
repeated
drug
administration,
antagonist-binding
site
remains
intact
when
needed,
ease
apply
multiple
GPCR.
This
may
applied
functional
proteins
other
than
Language: Английский
Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer’s Disease: Isoform-Specific Contributions
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 12299 - 12299
Published: Nov. 15, 2024
Oxidative
stress
is
linked
to
the
pathogenesis
of
Alzheimer's
disease
(AD),
a
neurodegenerative
disorder
marked
by
memory
impairment
and
cognitive
decline.
AD
characterized
accumulation
amyloid-beta
(Aβ)
plaques
formation
neurofibrillary
tangles
(NFTs)
hyperphosphorylated
tau.
associated
with
an
imbalance
in
redox
states
excessive
reactive
oxygen
species
(ROS).
Recent
studies
report
that
NADPH
oxidase
(NOX)
enzymes
are
significant
contributors
ROS
generation
diseases,
including
AD.
NOX-derived
aggravates
oxidative
neuroinflammation
during
In
this
review,
we
provide
potential
role
all
NOX
isoforms
their
respective
structural
involvement
progression,
highlighting
as
strategic
therapeutic
target.
A
comprehensive
understanding
inhibitors
could
valuable
insights
into
pathology
aid
development
targeted
treatments
for
Language: Английский
Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy—A State-of-the-Art Review
Olaf Rose,
No information about this author
Tim Croonenberg,
No information about this author
Stephanie Clemens
No information about this author
et al.
Antioxidants,
Journal Year:
2024,
Volume and Issue:
13(12), P. 1578 - 1578
Published: Dec. 21, 2024
Cisplatin
is
an
established
component
of
treatment
protocols
for
various
solid
malignancies
but
carries
a
significant
potential
serious
adverse
effects.
Ototoxicity
from
cisplatin
important
dose-limiting
toxicity
that
manifests
as
bilateral,
progressive,
irreversible,
dose-dependent
sensorineural
hearing
loss,
ear
pain,
tinnitus,
and
vestibular
dysfunction.
Despite
the
recent
approval
sodium
thiosulphate
prevention
cisplatin-induced
loss
(CIHL)
in
pediatric
patients,
structured
programs
are
not
routinely
implemented
most
hospitals,
reducing
platinum-induced
ototoxicity
adults
remains
clinical
problem
without
options.
Cochlear
oxidative
stress
plays
fundamental
role
CIHL.
Here,
we
review
molecular
mechanisms
leading
to
CIHL
preclinical
studies
testing
antioxidants
guide
future
trials
assessing
efficacy
safety
candidate
antioxidant
compounds
this
setting.
Language: Английский