Redox regulation: mechanisms, biology and therapeutic targets in diseases
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 7, 2025
Redox
signaling
acts
as
a
critical
mediator
in
the
dynamic
interactions
between
organisms
and
their
external
environment,
profoundly
influencing
both
onset
progression
of
various
diseases.
Under
physiological
conditions,
oxidative
free
radicals
generated
by
mitochondrial
respiratory
chain,
endoplasmic
reticulum,
NADPH
oxidases
can
be
effectively
neutralized
NRF2-mediated
antioxidant
responses.
These
responses
elevate
synthesis
superoxide
dismutase
(SOD),
catalase,
well
key
molecules
like
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
glutathione
(GSH),
thereby
maintaining
cellular
redox
homeostasis.
Disruption
this
finely
tuned
equilibrium
is
closely
linked
to
pathogenesis
wide
range
Recent
advances
have
broadened
our
understanding
molecular
mechanisms
underpinning
dysregulation,
highlighting
pivotal
roles
genomic
instability,
epigenetic
modifications,
protein
degradation,
metabolic
reprogramming.
findings
provide
foundation
for
exploring
regulation
mechanistic
basis
improving
therapeutic
strategies.
While
antioxidant-based
therapies
shown
early
promise
conditions
where
stress
plays
primary
pathological
role,
efficacy
diseases
characterized
complex,
multifactorial
etiologies
remains
controversial.
A
deeper,
context-specific
signaling,
particularly
redox-sensitive
proteins,
designing
targeted
aimed
at
re-establishing
balance.
Emerging
small
molecule
inhibitors
that
target
specific
cysteine
residues
proteins
demonstrated
promising
preclinical
outcomes,
setting
stage
forthcoming
clinical
trials.
In
review,
we
summarize
current
intricate
relationship
disease
also
discuss
how
these
insights
leveraged
optimize
strategies
practice.
Язык: Английский
Ferulic acid production in Escherichia coli by engineering caffeic acid O-methyltransferase
International Journal of Biological Macromolecules,
Год журнала:
2025,
Номер
306, С. 141764 - 141764
Опубликована: Март 4, 2025
Язык: Английский
Fluorogenic, Subsingle-Turnover Monitoring of Enzymatic Reactions Involving NAD(P)H Provides a Generalized Platform for Directed Ultrahigh-Throughput Evolution of Biocatalysts in Microdroplets
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
Enzyme
engineering
and
discovery
are
crucial
for
a
sustainable
future
bioeconomy.
Harvesting
new
biocatalysts
from
large
libraries
through
directed
evolution
or
functional
metagenomics
requires
accessible,
rapid
assays.
Ultrahigh-throughput
screening
formats
often
require
optical
readouts,
leading
to
the
use
of
model
substrates
that
may
misreport
target
activity
necessitate
bespoke
synthesis.
This
is
particular
challenge
when
glycosyl
hydrolases,
which
leverage
molecular
recognition
beyond
glycosidic
bond,
so
complex
chemical
synthesis
would
have
be
deployed
build
fluoro-
chromogenic
substrate.
In
contrast,
coupled
assays
represent
modular
"plug-and-play"
system:
any
enzyme–substrate
pairing
can
investigated,
provided
reaction
produce
common
intermediate
links
catalytic
detection
cascade
readout.
Here,
we
establish
producing
fluorescent
readout
in
response
NAD(P)H
via
glutathione
reductase
subsequent
thiol-mediated
uncaging
reaction,
with
low
nanomolar
limit
plates.
Further
scaling
down
microfluidic
droplet
possible:
fluorophore
leakage-free
report
3
orders
magnitude-improved
sensitivity
compared
absorbance-based
systems,
resolution
361,000
product
molecules
per
droplet.
Our
approach
enables
nonfluorogenic
droplet-based
enrichments,
applicability
hydrolases
imine
reductases
(IREDs).
To
demonstrate
assay's
readiness
combinatorial
experiments,
one
round
was
performed
select
glycosidase
processing
natural
substrate,
beechwood
xylan,
improved
kinetic
parameters
pool
>106
mutagenized
sequences.
Язык: Английский
Quantitative detection and cellular imaging of hydrogen sulfide using a SERS probe based on AuAg nanocages
Biosensors and Bioelectronics,
Год журнала:
2025,
Номер
unknown, С. 117580 - 117580
Опубликована: Май 1, 2025
Язык: Английский
High‐Throughput Colorimetric Detection and Quantification of Indoles and Pyrroloindoles for Enzymatic Activity Determination
ChemCatChem,
Год журнала:
2024,
Номер
16(11)
Опубликована: Фев. 20, 2024
Abstract
Indoles
and
pyrroloindoles
are
structural
motifs
present
in
many
biologically
active
natural
products.
Multiple
classes
of
enzymes
catalyze
the
transformation
indoles
into
via
group
transfer
followed
by
intramolecular
cyclization,
such
as
peroxydases,
methyltransferases,
prenyltransferases.
Due
to
selective
introduction
a
stereogenic
center,
these
receive
increasing
attention
catalytic
tools
for
production
pharmacologically
relevant
compounds.
Two
new
colorimetric
assays
described
this
work,
which
allow
quantification
enzymatic
reactions
from
perspective
substrate
product.
For
substrates,
indole
assay
is
based
on
modified
version
Ehrlich
test,
with
use
light
driving
force
color
formation.
The
pyrroloindole
uses
cerium
sulfate
reagent
complementary
both
were
successfully
utilized
activity
determination
C3‐indole
methyltransferase.
They
can
facilitate
high‐throughput
screening
mutant
libraries,
offering
support
engineering
enzymes,
but
also
be
used
stand‐alone
methods
detection
Язык: Английский