Acta Pharmaceutica Sinica B,
Год журнала:
2022,
Номер
12(3), С. 1019 - 1040
Опубликована: Янв. 21, 2022
Alzheimer's
disease
(AD),
the
most
common
neurodegenerative
disorder,
is
characterized
by
memory
loss
and
cognitive
dysfunction.
The
accumulation
of
misfolded
protein
aggregates
including
amyloid
beta
(Aβ)
peptides
microtubule
associated
tau
(MAPT/tau)
in
neuronal
cells
are
hallmarks
AD.
So
far,
exact
underlying
mechanisms
for
aetiologies
AD
have
not
been
fully
understood
effective
treatment
limited.
Autophagy
an
evolutionarily
conserved
cellular
catabolic
process
which
damaged
organelles
degraded
via
lysosomes.
Recently,
there
accumulating
evidence
linking
impairment
autophagy-lysosomal
pathway
with
pathogenesis.
Interestingly,
enhancement
autophagy
to
remove
has
proposed
as
a
promising
therapeutic
strategy
Here,
we
first
summarize
recent
genetic,
pathological
experimental
studies
regarding
We
then
describe
interplay
between
two
proteins,
Aβ
MAPT/tau,
Finally,
discuss
potential
strategies
small
molecules
that
target
both
animal
models
clinical
trials.
Overall,
this
article
highlights
pivotal
functions
pathogenesis
druggable
targets
treatment.
Cancer Discovery,
Год журнала:
2019,
Номер
9(9), С. 1167 - 1181
Опубликована: Авг. 21, 2019
Abstract
Autophagy,
a
multistep
lysosomal
degradation
pathway
that
supports
nutrient
recycling
and
metabolic
adaptation,
has
been
implicated
as
process
regulates
cancer.
Although
autophagy
induction
may
limit
the
development
of
tumors,
evidence
in
mouse
models
demonstrates
inhibition
can
growth
established
tumors
improve
response
to
cancer
therapeutics.
Certain
genotypes
be
especially
prone
inhibition.
Different
strategies
for
modulation
needed
depending
on
context.
Here,
we
review
new
advances
molecular
control
autophagy,
role
selective
cancer,
within
tumor
microenvironment
immunity.
We
also
highlight
clinical
efforts
repurpose
inhibitors,
such
hydroxychloroquine,
anticancer
agents
block
well
more
potent
specific
inhibitors
treatment,
future
directions
research.
Significance:
Autophagy
plays
complex
but
an
effective
therapeutic
strategy
advanced
A
deeper
understanding
enabled
novel
trial
strategies.
Challenges
opportunities
remain
identify
patients
most
likely
benefit
from
this
approach.
Genes & Development,
Год журнала:
2019,
Номер
33(15-16), С. 983 - 1007
Опубликована: Май 23, 2019
All
transcription
factors
are
equal,
but
some
more
equal
than
others.
In
the
25
yr
since
gene
encoding
microphthalmia-associated
factor
(MITF)
was
first
isolated,
MITF
has
emerged
as
a
key
coordinator
of
many
aspects
melanocyte
and
melanoma
biology.
Like
all
factors,
binds
to
specific
DNA
sequences
up-regulates
or
down-regulates
its
target
genes.
What
marks
being
remarkable
among
peers
is
sheer
range
biological
processes
that
it
appears
coordinate.
These
include
cell
survival,
differentiation,
proliferation,
invasion,
senescence,
metabolism,
damage
repair.
this
article
we
present
our
current
understanding
MITF's
role
regulation
in
development
disease,
well
those
MITF-related
TFEB
TFE3,
highlight
areas
where
knowledge
function
limited.
Cells,
Год журнала:
2018,
Номер
7(12), С. 278 - 278
Опубликована: Дек. 19, 2018
Autophagy
is
a
lysosome-dependent
cellular
degradation
program
that
responds
to
variety
of
environmental
and
stresses.
It
an
evolutionarily
well-conserved
essential
pathway
maintain
homeostasis,
therefore,
dysfunction
autophagy
closely
associated
with
wide
spectrum
human
pathophysiological
conditions
including
cancers
neurodegenerative
diseases.
The
discovery
characterization
the
kingdom
proteins
have
uncovered
molecular
basis
process.
In
addition,
recent
advances
on
various
post-translational
modifications
shed
light
multiple
layers
regulatory
mechanisms,
provide
novel
therapeutic
targets
for
treatment
The Journal of Cell Biology,
Год журнала:
2021,
Номер
220(6)
Опубликована: Апрель 20, 2021
Lysosomes
are
degradation
centers
and
signaling
hubs
in
cells
play
important
roles
cellular
homeostasis,
development,
aging.
Changes
lysosome
function
essential
to
support
adaptation
multiple
signals
stimuli.
Therefore,
biogenesis
activity
regulated
by
a
wide
variety
of
intra-
extracellular
cues.
Here,
we
summarize
current
knowledge
the
regulatory
mechanisms
biogenesis,
including
synthesis
lysosomal
proteins
their
delivery
via
endosome–lysosome
pathway,
reformation
lysosomes
from
degradative
vesicles,
transcriptional
regulation
genes.
We
survey
response
nutrient
nonnutrient
signals,
cell
cycle,
stem
quiescence,
fate
determination.
Finally,
discuss
functions
context
organismal
development
Autophagy,
Год журнала:
2021,
Номер
18(1), С. 86 - 103
Опубликована: Апрель 27, 2021
Macroautophagy/autophagy
is
a
cellular
catabolic
process
that
results
in
lysosome-mediated
recycling
of
organelles
and
protein
aggregates,
as
well
the
destruction
intracellular
pathogens.
Its
role
maintenance
intestinal
epithelium
particular
interest,
several
autophagy-related
genes
have
been
associated
with
disease.
Autophagy
its
regulatory
mechanisms
are
involved
both
homeostasis
repair
intestine,
supporting
barrier
function
response
to
stress
through
tight
junction
regulation
protection
from
cell
death.
Furthermore,
clear
has
emerged
for
autophagy
not
only
secretory
cells
but
also
stem
cells,
where
it
affects
their
metabolism,
proliferative
regenerative
capacity.
Here,
we
review
physiological
context
epithelial
how
genetic
mutations
affecting
contribute
development
