Frontiers in Immunology,
Год журнала:
2022,
Номер
12
Опубликована: Янв. 10, 2022
Neuronal
death
and
inflammatory
response
are
two
common
pathological
hallmarks
of
acute
central
nervous
system
injury
chronic
degenerative
disorders,
both
which
closely
related
to
cognitive
motor
dysfunction
associated
with
various
neurological
diseases.
Neurological
diseases
highly
heterogeneous;
however,
they
share
a
pathogenesis,
that
is,
the
aberrant
accumulation
misfolded/unfolded
proteins
within
endoplasmic
reticulum
(ER).
Fortunately,
cell
has
intrinsic
quality
control
mechanisms
maintain
proteostasis
network,
such
as
chaperone-mediated
folding
ER-associated
degradation.
However,
when
these
fail,
accumulate
in
ER
lumen
contribute
stress.
stress
been
implicated
nearly
all
initiates
unfolded
protein
restore
proteostasis,
if
damage
is
irreversible,
it
elicits
intracellular
cascades
inflammation.
With
growing
appreciation
functional
association
between
improved
understanding
multiple
underlying
molecular
mechanisms,
pharmacological
genetic
targeting
beginning
emerge
therapeutic
approaches
for
Hepatology,
Год журнала:
2022,
Номер
77(2), С. 619 - 639
Опубликована: Май 7, 2022
The
endoplasmic
reticulum
(ER)
is
an
intracellular
organelle
that
fosters
the
correct
folding
of
linear
polypeptides
and
proteins,
a
process
tightly
governed
by
ER‐resident
enzymes
chaperones.
Failure
to
shape
proper
3‐dimensional
architecture
proteins
culminates
in
accumulation
misfolded
or
unfolded
within
ER,
disturbs
ER
homeostasis,
leads
canonically
defined
stress.
Recent
studies
have
elucidated
cellular
perturbations,
such
as
lipotoxicity,
can
also
lead
In
response
stress,
protein
(UPR)
activated
reestablish
homeostasis
(“adaptive
UPR”),
or,
conversely,
provoke
cell
death
when
stress
overwhelmed
sustained
(“maladaptive
UPR”).
It
well
documented
contributes
onset
progression
multiple
hepatic
pathologies
including
NAFLD,
alcohol‐associated
liver
disease,
viral
hepatitis,
ischemia,
drug
toxicity,
cancers.
Here,
we
review
key
dealing
with
emerging
role
UPR
pathophysiology
diseases
from
cellular,
murine,
human
models.
Specifically,
will
summarize
current
available
knowledge
on
pharmacological
non‐pharmacological
interventions
may
be
used
target
maladaptive
for
treatment
nonmalignant
diseases.
Cell Death and Disease,
Год журнала:
2022,
Номер
13(8)
Опубликована: Авг. 15, 2022
Abstract
Alzheimer’s
disease
(AD)
is
a
devastating
neurodegenerative
disorder
characterized
by
gradual
loss
of
memory
and
cognitive
function,
which
constitutes
heavy
burden
on
the
healthcare
system
globally.
Current
therapeutics
to
interfere
with
underlying
process
in
AD
still
under
development.
Although
many
efforts
have
centered
toxic
forms
Aβ
effectively
tackle
AD,
considering
unsatisfactory
results
so
far
it
vital
examine
other
targets
therapeutic
approaches
as
well.
The
endoplasmic
reticulum
(ER)
stress
refers
build-up
unfolded
or
misfolded
proteins
within
ER,
thus,
perturbing
ER
cellular
homeostasis.
Emerging
evidence
indicates
that
contributes
onset
development
AD.
A
thorough
elucidation
machinery
pathology
may
help
open
up
new
avenues
management
this
condition
relieve
dementia
symptoms.
Herein,
we
aim
at
deciphering
unique
role
pathogenesis,
reviewing
key
findings,
existing
controversy
an
attempt
summarize
plausible
interventions
pathophysiology.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2021,
Номер
40(1)
Опубликована: Янв. 11, 2021
Abstract
Solid
tumors
often
grow
in
a
micro-environment
characterized
by
<
2%
O
2
tension.
This
condition,
together
with
the
aberrant
activation
of
specific
oncogenic
patwhays,
increases
amount
and
activity
hypoxia-inducible
factor-1α
(HIF-1α),
transcription
factor
that
controls
up
to
200
genes
involved
neoangiogenesis,
metabolic
rewiring,
invasion
drug
resistance.
Hypoxia
also
induces
endoplasmic
reticulum
(ER)
stress,
condition
triggers
cell
death,
if
cells
are
irreversibly
damaged,
or
survival,
stress
is
mild.
chronic
ER
both
induce
chemoresistance.
In
this
review
we
discuss
multiple
interconnected
circuitries
link
hypoxic
environment,
We
suggest
hypoxia
train
select
more
adapted
survive
unfavorable
conditions,
activating
pleiotropic
mechanisms
including
apoptosis
inhibition,
anti-oxidant
defences,
drugs
efflux.
adaptative
process
unequivocally
expands
clones
acquire
resistance
chemotherapy.
believe
pharmacological
inhibitors
HIF-1α
modulators
although
low
specificty
anti-cancer
efficacy
when
used
as
single
agents,
may
be
repurposed
chemosensitizers
against
chemorefractory
next
future.
