Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: June 14, 2024
The
endoplasmic
reticulum
(ER)
is
a
crucial
organelle
that
orchestrates
key
cellular
functions
like
protein
folding
and
lipid
biosynthesis.
However,
it
highly
sensitive
to
disturbances
lead
ER
stress.
In
response,
the
unfolded
response
(UPR)
activates
restore
homeostasis,
primarily
through
three
sensors:
IRE1,
ATF6,
PERK.
ERAD
autophagy
are
in
mitigating
stress,
yet
their
dysregulation
can
accumulation
of
misfolded
proteins.
Cisplatin,
commonly
used
chemotherapy
drug,
induces
stress
tumor
cells,
activating
complex
signaling
pathways.
Resistance
cisplatin
stems
from
reduced
drug
accumulation,
activation
DNA
repair,
anti-apoptotic
mechanisms.
Notably,
cisplatin-induced
dualistically
affect
promoting
either
survival
or
apoptosis,
depending
on
context.
for
degrading
proteins,
whereas
protect
cells
apoptosis
enhance
stress-induced
apoptosis.
interaction
between
resistance,
ERAD,
opens
new
avenues
cancer
treatment.
Understanding
these
processes
could
innovative
strategies
overcome
chemoresistance,
potentially
improving
outcomes
cisplatin-based
treatments.
This
comprehensive
review
provides
multifaceted
perspective
mechanisms
implications
therapy.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(18)
Published: Feb. 6, 2023
The
spatiotemporal
characterization
of
signaling
crosstalk
between
subcellular
organelles
is
crucial
for
the
therapeutic
effect
malignant
tumors.
Blocking
interactive
in
this
fashion
significant
but
challenging.
Herein,
a
communication
interception
strategy
reported,
which
blocks
cancer
therapy
with
underlying
molecular
mechanisms.
Briefly,
amorphous-core@crystalline-shell
Fe@Fe3
O4
nanoparticles
(ACFeNPs)
are
fabricated
to
specifically
block
lysosomes
and
endoplasmic
reticulum
(ER)
by
hydroxyl
radicals
generated
along
their
trajectory
through
heterogeneous
Fenton
reaction.
ACFeNPs
initially
enter
trigger
autophagy,
then
continuous
lysosomal
damage
generation
functional
autolysosomes,
mediates
ER-lysosome
crosstalk,
thus
autophagy
paralyzed.
Thereafter,
released
from
induce
ER
stress.
Without
alleviation
ER-stress-associated
apoptotic
pathway
fully
activated,
resulting
remarkable
effect.
This
provides
wide
venue
nanomedicine
exert
biological
advantages
confers
new
perspective
design
novel
anticancer
drugs.
Neural Regeneration Research,
Journal Year:
2023,
Volume and Issue:
19(5), P. 998 - 1005
Published: Sept. 22, 2023
Mitochondria
are
critical
cellular
energy
resources
and
central
to
the
life
of
neuron.
Mitophagy
selectively
clears
damaged
or
dysfunctional
mitochondria
through
autophagic
machinery
maintain
mitochondrial
quality
control
homeostasis.
Mature
neurons
postmitotic
consume
substantial
energy,
thus
require
highly
efficient
mitophagy
pathways
turn
over
mitochondria.
Recent
evidence
indicates
that
is
pivotal
pathogenesis
neurological
diseases.
However,
more
work
needed
study
pathway
components
as
potential
therapeutic
targets.
In
this
review,
we
briefly
discuss
characteristics
nonselective
autophagy
selective
autophagy,
including
ERphagy,
aggrephagy,
mitophagy.
We
then
introduce
mechanisms
Parkin-dependent
Parkin-independent
under
physiological
conditions.
Next,
summarize
diverse
repertoire
membrane
receptors
phospholipids
mediate
Importantly,
review
role
in
neurodegenerative
diseases
Alzheimer's
disease,
Parkinson's
amyotrophic
lateral
sclerosis.
Last,
recent
studies
considering
a
target
for
treating
Together,
our
may
provide
novel
views
better
understand
roles
disease
pathogenesis.
Molecular Cell,
Journal Year:
2023,
Volume and Issue:
84(1), P. 156 - 169
Published: Dec. 22, 2023
Ubiquitin-fold
modifier
1
(UFM1)
is
a
ubiquitin-like
protein
covalently
conjugated
with
intracellular
proteins
through
UFMylation,
process
similar
to
ubiquitylation.
Growing
lines
of
evidence
regarding
not
only
the
structural
basis
components
essential
for
UFMylation
but
also
their
biological
properties
shed
light
on
crucial
roles
UFM1
system
in
endoplasmic
reticulum
(ER),
such
as
ER-phagy
and
ribosome-associated
quality
control
at
ER,
although
there
are
some
functions
unrelated
ER.
Mouse
genetics
studies
revealed
indispensable
this
hematopoiesis,
liver
development,
neurogenesis,
chondrogenesis.
Of
critical
importance,
mutations
genes
encoding
core
humans
cause
hereditary
developmental
epileptic
encephalopathy
Schohat-type
osteochondrodysplasia
epiphysis.
Here,
we
provide
multidisciplinary
review
our
current
understanding
mechanisms
cellular
well
its
pathophysiological
roles,
discuss
issues
that
require
resolution.
Developmental Cell,
Journal Year:
2024,
Volume and Issue:
59(16), P. 2035 - 2052.e10
Published: Aug. 1, 2024
Protein
biogenesis
within
the
endoplasmic
reticulum
(ER)
is
crucial
for
organismal
function.
Errors
during
protein
folding
necessitate
removal
of
faulty
products.
ER-associated
degradation
and
ER-phagy
target
misfolded
proteins
proteasomal
lysosomal
degradation.
The
mechanisms
initiating
in
response
to
ER
proteostasis
defects
are
not
well
understood.
By
studying
mouse
primary
cells
patient
samples
as
a
model
storage
disorders
(ERSDs),
we
show
that
accumulation
products
triggers
involving
SESTRIN2,
nutrient
sensor
controlling
mTORC1
signaling.
SESTRIN2
induction
by
XBP1
inhibits
mTORC1's
phosphorylation
TFEB/TFE3,
allowing
these
transcription
factors
enter
nucleus
upregulate
receptor
FAM134B
along
with
genes.
This
promotes
via
FAM134B-Calnexin
complex.
Pharmacological
improves
clearance
ERSDs.
Our
study
identifies
interplay
between
signaling
quality
control,
suggesting
therapeutic
strategies
Advanced Functional Materials,
Journal Year:
2024,
Volume and Issue:
34(18)
Published: Jan. 23, 2024
Abstract
Currently,
the
understanding
of
cyclic
GMP‐AMP
synthase
(cGAS)‐stimulator
interferon
genes
(STING)
pathway's
involvement
in
efficient
immunotherapy
mainly
revolves
around
role
mitochondria
or
nucleus
modulation.
Nonetheless,
endoplasmic
reticulum
(ER)
stress
activating
cGAS‐STING
mechanism
to
boost
immunity
against
tumors
remains
essentially
unexplored.
Herein,
novel
findings
demonstrating
that
ER
can
be
used
as
a
strategy
for
stimulating
pathway,
thereby
augmenting
immune
response
cancer,
are
presented.
To
accomplish
this
objective,
ER‐targeting
p
‐methylbenzene
sulfonamide‐tailored
IR780
(p‐780)
is
synthesized
and
it
loaded
into
CaO
2
nanoparticles,
which
further
functionalized
with
distearoyl
phosphoethanolamine‐polyethylene
glycol（DSPE‐PEG）‐biotin
form
PEG/CaO
@p‐780
NPs.
The
disruption
calcium
homeostasis,
coupled
heightened
levels
reactive
oxygen
species
(ROS)
mediated
by
p‐780,
along
hyperpyrexia,
collectively
contributes
amplification
stress.
This
cascade
events
effectively
triggers
pathway
and,
parallel,
facilitates
degradation
programmed
cell
death
1
ligand
(PD‐L1)
protein.
In
addition,
released
through
decomposition
expected
promote
p‐780–mediated
phototherapy,
while
reversing
immunosuppressive
tumor
microenvironment
associated
hypoxia.
Furthermore,
DSPE‐PEG‐biotin
site‐specific
drug
delivery
active
targeting
biotin
receptor.
Collectively,
nanoparticles
successfully
activate
systemic
antitumor
enhancing
