Cellular and Molecular Life Sciences,
Journal Year:
2024,
Volume and Issue:
81(1)
Published: July 6, 2024
Orexinergic
neurons
are
critically
involved
in
regulating
arousal,
wakefulness,
and
appetite.
Their
dysfunction
has
been
associated
with
sleeping
disorders,
non-peptide
drugs
currently
being
developed
to
treat
insomnia
narcolepsy.
Yet,
no
light-regulated
agents
available
reversibly
control
their
activity.
To
meet
this
need,
a
photoswitchable
peptide
analogue
of
the
endogenous
neuroexcitatory
orexin-B
was
designed,
synthesized,
tested
vitro
vivo.
This
compound
-
photorexin
is
first
photo-reversible
ligand
reported
for
orexin
receptors.
It
allows
dynamic
activity
(including
almost
same
efficacy
as
orexin-B,
high
nanomolar
potency,
subtype
selectivity
human
OX
PNAS Nexus,
Journal Year:
2025,
Volume and Issue:
4(2)
Published: Jan. 15, 2025
Abstract
Acetylcholine
and
the
cholinergic
system
are
crucial
to
brain
function,
including
functions
such
as
consciousness
cognition.
Dysregulation
of
this
is
implicated
in
pathophysiology
neurological
conditions
Alzheimer's
disease.
For
reason,
neuromodulation
relevant
both
basic
neuroscience
clinical
neurology.
In
study,
we
used
photopharmacology
modulate
neuronal
activity
using
novel
selective
type-1
muscarinic
(M1)
photoswitchable
drugs:
agonist
benzyl
quinolone
carboxylic
acid-azo-iperoxo
(BAI)
antagonist
cryptozepine-2.
Our
aim
was
investigate
control
over
these
receptors
light
effects
drugs
on
physiological
spontaneous
slow
waves
epileptic
cerebral
cortex.
First,
transfected
HEK
cell
cultures
demonstrated
BAI’s
preferential
activation
M1
acetylcholine
(mAChRs)
compared
with
M2
mAChRs.
Next,
found
that
white-light
illumination
BAI
increased
frequency
slow-wave
cortical
networks
active
slices
anesthetized
mice,
through
M1-mAChRs
activation.
Illumination
cryptozepine-2
UV
effectively
suppressed
not
only
muscarinic-induced
increase
frequency,
but
also
epileptiform
discharges.
These
findings
shed
role
network
dynamics
lay
groundwork
for
developing
advanced
light-based
pharmacological
therapies.
Photopharmacology
offers
potential
high-precision
spatiotemporal
high
specificity
healthy
pathological
conditions.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(38)
Published: June 18, 2024
A
problem
of
systemic
pharmacotherapy
is
off-target
activity,
which
causes
adverse
effects.
Outstanding
examples
include
neuroinhibitory
medications
like
antiseizure
drugs,
are
used
against
epilepsy
and
neuropathic
pain
but
cause
side
There
a
need
drugs
that
inhibit
nerve
signals
locally
on-demand
without
affecting
other
regions
the
body.
Photopharmacology
aims
to
address
this
with
light-activated
localized
illumination
in
target
organ.
Here,
we
have
developed
photoswitchable
derivatives
widely
prescribed
drug
carbamazepine.
For
purpose,
expanded
our
method
ortho
azologization
tricyclic
meta/para
N-bridged
diazocine.
Our
results
validate
concept
cryptoazologs
(uniquely
exemplified
by
Carbazopine-1)
bring
light
Carbadiazocine
(8),
can
be
photoswitched
between
400-590
nm
(using
violet
LEDs
halogen
lamps)
shows
good
drug-likeness
predicted
safety.
Both
compounds
display
activity
vitro
translucent
zebrafish
larvae.
(8)
also
offers
vivo
analgesic
efficacy
(mechanical
thermal
stimuli)
rat
model
simple
compelling
treatment
demonstration
non-invasive
illumination.
Medicinal Research Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 6, 2025
The
use
of
photoswitchable
ligand
to
control
the
protein
functionalities
and
related
downstream
effects
in
an
on-off
manner
is
active
research
area
photopharmacology
medicinal
chemistry.
Temporal
grants
a
privilege
identify
crucial
role
particular
receptor
biological
occurrences
without
destroying
permanently.
Additionally,
light
can
be
applied
site-selectively
regulate
functionality
with
cellular
sub-cellular
levels
spatial
resolutions.
spatiotemporal
resolution
enables
probing
specific
receptor,
isoform,
or
signalling
pathway.
This
reversible
fast
highly
beneficial
studying
dynamic
processes,
including
but
not
limited
signal
transduction,
neurotransmission,
cell
divisions,
immune
response,
folding,
degradation.
Though
several
light-active
ligands
have
been
developed
efficiently,
only
few
reports
on
exist
literature.
Major
challenges
achieve
efficient
photoswitches
study
are
synthesis
strategy,
photostability
ligand,
bidirectional
visible
switching
ability
most
importantly
precise
controlling
local
concentration
desired
photoisomer
using
light.
site-specific
localization
depends
multiple
factors
like
nature
photoswitch,
binding
affinity
both
photoisomers,
molecular
diffusion
irradiation
conditions.
present
review
discusses
suitable
techniques
different
achieving
subcellular
dimension
functionality.
Multiple
strategies
discussed,
along
their
advantages
limitations,
explore
enormous
potentiality
these
approaches
manipulating
Medicinal Research Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 23, 2025
ABSTRACT
Cholinergic
transmission
plays
a
critical
role
in
both
the
central
and
peripheral
nervous
systems,
affecting
processes
such
as
learning,
memory,
inflammation.
Conventional
cholinergic
drugs
generally
suffer
from
poor
selectivity
temporal
precision,
leading
to
undesired
effects
limited
therapeutic
efficacy.
Photopharmacology
aims
overcome
limitations
of
traditional
using
photocleavable
or
photoswitchable
ligands
spatiotemporal
patterns
illumination.
Spanning
muscarinic
nicotinic
modulators
cholinesterase
inhibitors,
this
review
explores
development
application
light‐activated
compounds
tools
for
unraveling
signaling
physiological
pathological
contexts,
while
also
paving
way
innovative
phototherapeutic
approaches.
Interdisciplinary materials,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 7, 2024
Abstract
Three‐photon
fluorescence
(3PF)
imaging
is
an
emerging
technology
for
deep‐tissue
submicroscopic
structures
by
nonlinearly
redshifting
the
excitation
wavelength
to
second
near‐infrared
(NIR‐II)
window;
thus,
this
approach
has
great
advantages,
including
deep
penetration
depth,
good
spatial
resolution,
low
background,
and
a
high
signal‐to‐noise
ratio.
3PF
been
demonstrated
be
powerful
tool
noninvasively
visualizing
all
kinds
of
tissues
in
recent
years.
Benefiting
from
excellent
biosecurity
structural
controllability,
development
organic
probes
highly
important
advancing
vivo.
However,
there
no
summary
generalizability
design
progress
probes.
Herein,
review
introduces
fundamental
principle
highlights
advantages
bioimaging.
The
molecular
these
also
summarized
based
on
relative
optical
indices.
Furthermore,
different
application
scenarios
are
listed
detail.
In
end,
main
challenges,
significance
probe
exploitation,
prospective
orientation
precise
proposed
discussed
promoting
future
applications
clinical
translation.
Brain Communications,
Journal Year:
2024,
Volume and Issue:
6(5)
Published: Jan. 1, 2024
Abstract
Experimental
and
clinical
studies
of
consciousness
identify
brain
states
(i.e.
quasi-stable
functional
cerebral
organization)
in
a
non-systematic
manner
largely
independent
the
research
into
state
modulation.
In
this
narrative
review,
we
synthesize
advances
identification
associated
with
animal
models
physiological
(sleep),
pharmacological
(anaesthesia)
pathological
(disorders
consciousness)
altered
humans.
We
show
that
reduced
frequencies
which
operates
are
slowed
down
pattern
communication
is
sparser,
less
efficient,
complex.
The
results
also
highlight
damaged
resting-state
networks,
particular
default
mode
network,
decreased
connectivity
long-range
connections
especially
thalamocortical
loops.
Next,
therapeutic
approaches
to
treat
disorders
consciousness,
through
pharmacology
(e.g.
amantadine,
zolpidem),
(non-)
invasive
stimulation
transcranial
direct
current
stimulation,
deep
stimulation)
have
shown
partial
effectiveness
promoting
recovery.
Although
some
features
conscious
may
improve
response
neuromodulation,
targeting
often
remains
non-specific
does
not
always
lead
(behavioural)
improvements.
fields
neuromodulation
relation
showing
fascinating
developments
that,
when
integrated,
might
propel
development
new
better-targeted
techniques
for
consciousness.
here
propose
framework
modulation
facilitate
interaction
between
two
fields.
should
be
identified
predictive
setting,
followed
by
theoretical
empirical
testing
models,
under
anaesthesia
patients
disorder
promote
line
such
predictions.
This
further
helps
where
challenges
opportunities
lay
maturation
context
It
will
become
apparent
one
angle
opportunity
provided
addition
computational
modelling.
Finally,
it
aids
recognizing
possibilities
obstacles
translation
these
diagnostic
treatment
options
across
both
multimodal
multi-species
outlined
throughout
review.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(38)
Published: June 18, 2024
Abstract
A
problem
of
systemic
pharmacotherapy
is
off‐target
activity,
which
causes
adverse
effects.
Outstanding
examples
include
neuroinhibitory
medications
like
antiseizure
drugs,
are
used
against
epilepsy
and
neuropathic
pain
but
cause
side
There
a
need
drugs
that
inhibit
nerve
signals
locally
on‐demand
without
affecting
other
regions
the
body.
Photopharmacology
aims
to
address
this
with
light‐activated
localized
illumination
in
target
organ.
Here,
we
have
developed
photoswitchable
derivatives
widely
prescribed
drug
carbamazepine.
For
purpose,
expanded
our
method
ortho
azologization
tricyclic
meta
/
para
N‐bridged
diazocine.
Our
results
validate
concept
cryptoazologs
(uniquely
exemplified
by
Carbazopine‐
1
)
bring
light
Carbadiazocine
(
8
),
can
be
photoswitched
between
400–590
nm
(using
violet
LEDs
halogen
lamps)
shows
good
drug‐likeness
predicted
safety.
Both
compounds
display
activity
vitro
translucent
zebrafish
larvae.
also
offers
vivo
analgesic
efficacy
(mechanical
thermal
stimuli)
rat
model
simple
compelling
treatment
demonstration
non‐invasive
illumination.
Molecules,
Journal Year:
2024,
Volume and Issue:
29(19), P. 4523 - 4523
Published: Sept. 24, 2024
Photoregulation
of
biomolecules
has
become
crucial
tools
in
chemical
biology,
because
light
enables
access
under
mild
conditions
and
with
delicate
spatiotemporal
control.
The
control
enzyme
activity
a
reversible
way
is
challenge.
To
achieve
it,
facile
approach
to
use
photoswitchable
inhibitors.
This
review
highlights
recent
progress
inhibitors
based
on
azobenzenes
units.
suggests
that
the
incorporation
an
azobenzene
unit
known
inhibitor
effective
method
for
preparing
inhibitor,
these
inhibitors,
enzymes
can
be
regulated
by
optical
control,
which
valuable
both
basic
science
therapeutic
applications.
Orexinergic
neurons
are
critically
involved
in
regulating
arousal,
wakefulness,
and
appetite.
Their
dysfunction
has
been
associated
with
sleeping
disorders,
non-peptide
drugs
currently
being
developed
to
treat
insomnia
narcolepsy.
Yet,
no
light-regulated
agents
available
reversibly
control
their
activity.
To
meet
this
need,
a
photoswitchable
peptide
analogue
of
the
endogenous
neuroexcitatory
orexin-B
was
designed,
synthesized,
tested
vitro
vivo.
This
compound
(photorexin)
is
first
photo-reversible
ligand
reported
for
orexin
receptors.
It
allows
dynamic
activity
(including
full
agonism,
nanomolar
activity,
subtype
selectivity
human
OX2
receptors)
vivo
zebrafish
larvae
by
direct
application
water.
Photorexin
induces
dose-
light-dependent
changes
locomotion
reduction
successive
induction
reflex
that
sleep
behavior.
Molecular
dynamics
calculations
indicate
trans
cis
photorexins
adopt
similar
bent
conformations
only
discriminant
between
structures
activities
positioning
N-terminus
at
extracellular
region
receptor.
Thus,
our
approach
could
be
extended
broad
important
family
neuropeptides
share
“message-address”
mechanism
when
binding
cognate
