Frontiers in Oncology,
Journal Year:
2021,
Volume and Issue:
11
Published: July 29, 2021
Over
decades
of
studies,
accumulating
evidence
has
suggested
that
epigenetic
dysregulation
is
a
hallmark
tumours.
Post-translational
modifications
histones
are
involved
in
tumour
pathogenesis
and
development
mainly
by
influencing
broad
range
physiological
processes.
Histone
deacetylases
(HDACs)
histone
acetyltransferases
(HATs)
pivotal
modulators
regulate
dynamic
processes
the
acetylation
at
lysine
residues,
thereby
transcription
oncogenes
suppressor
genes.
Moreover,
HDACs
mediate
deacetylation
process
many
nonhistone
proteins
thus
orchestrate
host
pathological
processes,
such
as
pathogenesis.
In
this
review,
we
elucidate
functions
cancer.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Aug. 13, 2022
Regulated
cell
death
(RCD),
also
well-known
as
programmed
(PCD),
refers
to
the
form
of
that
can
be
regulated
by
a
variety
biomacromolecules,
which
is
distinctive
from
accidental
(ACD).
Accumulating
evidence
has
revealed
RCD
subroutines
are
key
features
tumorigenesis,
may
ultimately
lead
establishment
different
potential
therapeutic
strategies.
Hitherto,
targeting
with
pharmacological
small-molecule
compounds
been
emerging
promising
avenue,
rapidly
progressed
in
many
types
human
cancers.
Thus,
this
review,
we
focus
on
summarizing
not
only
apoptotic
and
autophagy-dependent
signaling
pathways,
but
crucial
pathways
other
subroutines,
including
necroptosis,
pyroptosis,
ferroptosis,
parthanatos,
entosis,
NETosis
lysosome-dependent
(LCD)
cancer.
Moreover,
further
discuss
current
situation
several
improve
cancer
treatment,
such
single-target,
dual
or
multiple-target
compounds,
drug
combinations,
some
new
strategies
would
together
shed
light
future
directions
attack
vulnerabilities
drugs
for
purposes.
Theranostics,
Journal Year:
2020,
Volume and Issue:
10(18), P. 8315 - 8342
Published: Jan. 1, 2020
Sirtuin
3
(SIRT3)
is
one
of
the
most
prominent
deacetylases
that
can
regulate
acetylation
levels
in
mitochondria,
which
are
essential
for
eukaryotic
life
and
inextricably
linked
to
metabolism
multiple
organs.
Hitherto,
SIRT3
has
been
substantiated
be
involved
almost
all
aspects
mitochondrial
homeostasis,
protecting
mitochondria
from
a
variety
damage.
Accumulating
evidence
recently
documented
associated
with
many
types
human
diseases,
including
age-related
cancer,
heart
disease
metabolic
indicating
potential
therapeutic
target.
Here
we
focus
on
summarizing
intricate
mechanisms
recent
notable
advances
field
small-molecule
activators
or
inhibitors
targeting
as
well
their
applications
future
drug
discovery.
Oral Diseases,
Journal Year:
2021,
Volume and Issue:
28(3), P. 559 - 567
Published: Feb. 11, 2021
Oral
cancer
is
one
of
the
most
leading
responsible
for
significant
morbidity
and
mortality.
The
sirtuins
(SIRTs)
are
a
family
class
III
histone
deacetylases
known
to
regulate
variety
molecular
signaling
associated
with
different
types
including
oral
malignancies.
SIRT1
acts
as
bifunctional
in
cancer.
In
cancer,
seems
work
tumor
suppressor.
carcinogenic
potential
also
reported
hence,
its
role
still
ambiguous.
SIRT2
said
play
dual-faced
cancers.
However,
not
studied
remains
obscure.
SIRT3
expression
was
positively
correlated
studies
showed
anti-cancer
SIRT7
loss
observed
cells,
while
overexpression
caused
suppression
cells
proliferation,
migration,
invasiveness.
other
SIRTs
meagerly
or
reports
available.
To
date,
only
roles
SIRT1,
SIRT3,
have
been
Therefore,
understanding
regulatory
mechanisms
employed
by
modulate
important
developing
therapeutic
strategies.
Nature Metabolism,
Journal Year:
2023,
Volume and Issue:
5(5), P. 821 - 841
Published: May 15, 2023
Abstract
The
interplay
between
liver
and
bone
metabolism
remains
largely
uncharacterized.
Here,
we
uncover
a
mechanism
of
liver-bone
crosstalk
regulated
by
hepatocyte
SIRT2.
We
demonstrate
that
SIRT2
expression
is
increased
in
aged
mice
elderly
humans.
Liver-specific
deficiency
inhibits
osteoclastogenesis
alleviates
loss
mouse
models
osteoporosis.
identify
leucine-rich
α-2-glycoprotein
1
(LRG1)
as
functional
cargo
hepatocyte-derived
small
extracellular
vesicles
(sEVs).
In
SIRT2-deficient
hepatocytes,
LRG1
levels
sEVs
are
upregulated,
leading
to
transfer
bone-marrow-derived
monocytes
(BMDMs),
turn,
inhibition
osteoclast
differentiation
via
reduced
nuclear
translocation
NF-κB
p65.
Treatment
with
carrying
high
human
BMDMs
osteoporosis,
resulting
attenuated
mice.
Furthermore,
the
plasma
level
positively
correlated
mineral
density
Thus,
drugs
targeting
hepatocyte-osteoclast
communication
may
constitute
promising
therapeutic
strategy
for
primary
Journal of Hematology & Oncology,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: May 31, 2024
Abstract
Histone
deacetylase
(HDAC)
serves
as
a
critical
molecular
regulator
in
the
pathobiology
of
various
malignancies
and
have
garnered
attention
viable
target
for
therapeutic
intervention.
A
variety
HDAC
inhibitors
(HDACis)
been
developed
to
HDACs.
Many
preclinical
studies
conclusively
demonstrated
antitumor
effects
HDACis,
whether
used
monotherapy
or
combination
treatments.
On
this
basis,
researchers
conducted
clinical
evaluate
potential
selective
pan-HDACis
settings.
In
our
work,
we
extensively
summarized
organized
current
trials,
providing
comprehensive
overview
advancements
targeting
therapy.
Furthermore,
engaged
discussions
about
several
trials
that
did
not
yield
positive
outcomes,
analyzing
factors
led
their
lack
anticipated
effectiveness.
Apart
from
experimental
design
factors,
issues
such
toxicological
side
effects,
tumor
heterogeneity,
unexpected
off-target
also
contributed
these
less-than-expected
results.
These
challenges
naturally
become
significant
barriers
application
HDACis.
Despite
challenges,
believe
HDACi
research
improvements
therapies
will
pave
way
lead
broad
hopeful
future
treatment
solid
tumors.
Molecular Neurodegeneration,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: Jan. 15, 2025
Abstract
Background
Alzheimer’s
Disease
(AD)
is
a
neurodegenerative
disease
with
drastically
altered
astrocytic
metabolism.
Astrocytic
GABA
and
H
2
O
are
associated
memory
impairment
in
AD
synthesized
through
the
Monoamine
Oxidase
B
(MAOB)-mediated
multi-step
degradation
of
putrescine.
However,
enzymes
downstream
to
MAOB
this
pathway
remain
unidentified.
Methods
Using
transcriptomics
analysis,
we
identified
two
candidate
enzymes,
Aldehyde
Dehydrogenase
1
family
member
A1
(ALDH1A1)
Sirtuin
(SIRT2)
for
steps
following
production
pathway.
We
used
immunostaining,
metabolite
analysis
electrophysiology,
both
vitro
vivo,
confirm
participation
these
production.
checked
presence
SIRT2
human
patients
as
well
mouse
model
APP/PS1
finally,
selectively
ablated
astrocytes
mice
observe
its
effects
on
pathology.
Results
Immunostaining,
electrophysiology
recapitulated
ALDH1A1
Inhibition
reduced
but
not
,
key
molecule
neurodegeneration.
Elevated
expression
was
found
hippocampal
mice.
Astrocyte-specific
gene-silencing
restored
partially
improved
function.
Conclusions
Our
study
first
identify
specific
role
reactive
astrogliosis
determine
metabolic
step
catalyzed
by
enzyme.
partial,
yet
significant
process,
thereby
highlighting
new
players
findings
therefore,
offer
tool
segregate
from
production,
aiding
future
research
diseases.
Graphical
Journal of Cellular and Molecular Medicine,
Journal Year:
2019,
Volume and Issue:
24(1), P. 941 - 953
Published: Nov. 19, 2019
Abstract
Celastrol,
a
pentacyclic
tritepene
extracted
from
Tripterygium
Wilfordi
plant,
showing
potent
liver
protection
effects
on
several
liver‐related
diseases.
However,
the
anti‐inflammatory
potential
of
celastrol
in
fibrosis
and
detailed
mechanisms
remain
uncovered.
This
study
was
to
investigate
effect
further
reveal
celastrol‐induced
with
focus
AMPK‐SIRT3
signalling.
Celastrol
showed
ameliorative
both
activated
hepatic
stellate
cells
(HSCs)
fibrotic
liver.
remarkably
suppressed
inflammation
vivo
inhibited
secretion
inflammatory
factors
vitro.
Interestingly,
increased
SIRT3
promoter
activity
expression
HSCs.
Furthermore,
silencing
evidently
ameliorated
celastrol.
Besides,
we
found
that
could
increase
AMPK
phosphorylation.
Further
investigation
siRNA
decreased
but
had
no
obvious
phosphorylation
AMPK.
In
addition,
inhibition
by
employing
compound
C
(an
inhibitor)
or
AMPK1α
significantly
expression,
suggesting
an
up‐stream
protein
fibrosis.
We
depletion
attenuated
inhibitory
inflammation.
Collectively,
mainly
through
activating
signalling,
which
makes
be
candidate
treating
protecting
against
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: March 9, 2022
Abstract
The
age-dependent
decline
in
remyelination
potential
of
the
central
nervous
system
during
ageing
is
associated
with
a
declined
differentiation
capacity
oligodendrocyte
progenitor
cells
(OPCs).
molecular
players
that
can
enhance
OPC
or
rejuvenate
OPCs
are
unclear.
Here
we
show
that,
mouse
OPCs,
nuclear
entry
SIRT2
impaired
and
NAD
+
levels
reduced
ageing.
When
supplement
β-nicotinamide
mononucleotide
(β-NMN),
an
precursor,
differentiation,
were
rescued
aged
animals.
We
effects
on
myelination
mediated
via
-SIRT2-H3K18Ac-ID4
axis,
required
for
rejuvenating
OPCs.
Our
results
rescue
to
comparable
young
age,
providing
targets
