The Annual Review of Pharmacology and Toxicology,
Год журнала:
2023,
Номер
64(1), С. 527 - 550
Опубликована: Сен. 22, 2023
Drug
discovery
is
adapting
to
novel
technologies
such
as
data
science,
informatics,
and
artificial
intelligence
(AI)
accelerate
effective
treatment
development
while
reducing
costs
animal
experiments.
AI
transforming
drug
discovery,
indicated
by
increasing
interest
from
investors,
industrial
academic
scientists,
legislators.
Successful
requires
optimizing
properties
related
pharmacodynamics,
pharmacokinetics,
clinical
outcomes.
This
review
discusses
the
use
of
in
three
pillars
discovery:
diseases,
targets,
therapeutic
modalities,
with
a
focus
on
small
molecule
drugs.
technologies,
generative
chemistry,
machine
learning,
multi-property
optimization,
have
enabled
several
compounds
enter
trials.
The
scientific
community
must
carefully
vet
known
information
address
reproducibility
crisis.
full
potential
can
only
be
realized
sufficient
ground
truth
appropriate
human
intervention
at
later
pipeline
stages.
Autophagy,
Год журнала:
2022,
Номер
19(2), С. 388 - 400
Опубликована: Апрель 25, 2022
Age-related
macular
degeneration
(AMD)
is
the
leading
cause
of
visual
impairment
in
aging
population
with
limited
understanding
its
pathogenesis
and
a
lack
effective
treatment.
The
progression
AMD
initially
characterized
by
atrophic
alterations
retinal
pigment
epithelium,
as
well
formation
lysosomal
lipofuscin
extracellular
drusen
deposits.
Damage
caused
chronic
oxidative
stress,
protein
aggregation
inflammatory
processes
may
lead
to
geographic
atrophy
and/or
choroidal
neovascularization
fibrosis.
role
macroautophagy/autophagy
pathology
steadily
emerging.
This
review
describes
selective
secretory
autophagy
their
biogenesis,
senescence-associated
phenotype,
inflammation
epithelial-mesenchymal
transition
AMD.
Molecular Cell,
Год журнала:
2023,
Номер
83(19), С. 3404 - 3420
Опубликована: Окт. 1, 2023
Mitochondria
are
central
hubs
of
cellular
metabolism
that
also
play
key
roles
in
signaling
and
disease.
It
is
therefore
fundamentally
important
mitochondrial
quality
activity
tightly
regulated.
Mitochondrial
degradation
pathways
contribute
to
control
networks
can
regulate
the
metabolic
profile
mitochondria
ensure
homeostasis.
Here,
we
cover
many
varied
ways
which
cells
degrade
or
remove
their
unwanted
mitochondria,
ranging
from
mitophagy
extrusion.
The
molecular
signals
driving
these
discussed,
including
physiological
contexts
under
different
engaged.
Cell Death and Disease,
Год журнала:
2023,
Номер
14(7)
Опубликована: Июль 24, 2023
Abstract
Ferroptosis
is
a
recently
discovered
essential
type
of
cell
death
that
mainly
characterized
by
iron
overload
and
lipid
peroxidation.
Emerging
evidence
suggests
ferroptosis
double-edged
sword
in
human
cancer.
However,
the
precise
underlying
molecular
mechanisms
their
differential
roles
tumorigenesis
are
unclear.
Therefore,
this
review,
we
summarize
briefly
present
key
pathways
ferroptosis,
paying
special
attention
to
regulation
as
well
its
dual
role
an
oncogenic
tumor
suppressor
event
various
cancers.
Moreover,
multiple
pharmacological
activators
summarized,
prospect
targeting
cancer
therapy
further
elucidated.
Redox Biology,
Год журнала:
2022,
Номер
55, С. 102413 - 102413
Опубликована: Июль 31, 2022
Ferroptosis
is
a
newly
recognized
form
of
regulated
cell
death
that
characterized
by
severe
lipid
peroxidation
initiated
iron
overload
and
the
generation
reactive
oxygen
species
(ROS).
However,
role
in
ionizing
radiation
(IR)-induced
intestinal
injury
has
not
been
fully
illustrated
yet.
In
this
study,
we
found
IR
induced
ferroptosis
epithelial
cells,
as
indicated
increase
intracellular
levels
peroxidation,
upregulation
prostaglandin-endoperoxide
synthase
2
(PTGS2)
mRNA,
reduced
glutathione
peroxidase
4
(GPX4)
mRNA
(GSH)
levels,
significant
mitochondrial
damage.
addition,
chelator
deferoxamine
(DFO)
attenuated
IR-induced
vitro
vivo.
Intriguingly,
pharmacological
inhibition
autophagy
with
3-methyladenine
(3-MA)
mitigated
ferritin
downregulation,
ferroptosis.
increased
nuclear
receptor
coactivator
(NCOA4)
protein.
NCOA4
knockdown
significantly
inhibited
reduction
ferritin,
decreased
level
free
iron,
HIEC
indicating
NCOA4-mediated
autophagic
degradation
(ferritinophagy)
was
required
for
Furthermore,
cytoplasmic
further
activated
mitoferrin2
(Mfrn2)
on
membrane,
which
turn
transport
into
mitochondria,
resulting
ROS
production
mice
fed
an
iron-deficient
diet
3
weeks
showed
reversal
abdominal
exposure.
Taken
together,
novel
mechanism
cytotoxicity,
dependent
ferritinophagy.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Окт. 6, 2022
As
the
essential
regulators
of
organ
fibrosis,
macrophages
undergo
marked
phenotypic
and
functional
changes
after
injury.
These
in
macrophage
phenotype
function
can
result
maladaptive
repair,
causing
chronic
inflammation
development
pathological
fibrosis.
Autophagy,
a
highly
conserved
lysosomal
degradation
pathway,
is
one
major
players
to
maintain
homeostasis
through
clearing
protein
aggregates,
damaged
organelles,
invading
pathogens.
Emerging
evidence
has
shown
that
autophagy
plays
an
role
polarization,
inflammation,
Because
high
heterogeneity
different
organs,
types
may
play
roles
Here,
we
review
current
understanding
fibrosis
highlight
potential
treatment
Finally,
important
unresolved
issues
this
field
are
briefly
discussed.
A
better
mechanisms
contribute
developing
novel
therapies
for
inflammatory
diseases
