Cells,
Journal Year:
2023,
Volume and Issue:
12(6), P. 852 - 852
Published: March 9, 2023
Sirtuin
5
(SIRT5)
is
a
predominantly
mitochondrial
enzyme
catalyzing
the
removal
of
glutaryl,
succinyl,
malonyl,
and
acetyl
groups
from
lysine
residues
through
NAD+-dependent
deacylase
mechanism.
SIRT5
an
important
regulator
cellular
homeostasis
modulates
activity
proteins
involved
in
different
metabolic
pathways
such
as
glycolysis,
tricarboxylic
acid
(TCA)
cycle,
fatty
oxidation,
electron
transport
chain,
generation
ketone
bodies,
nitrogenous
waste
management,
reactive
oxygen
species
(ROS)
detoxification.
controls
wide
range
aspects
myocardial
energy
metabolism
plays
critical
roles
heart
physiology
stress
responses.
Moreover,
has
protective
function
context
neurodegenerative
diseases,
while
it
acts
context-dependent
tumor
promoter
or
suppressor.
In
addition,
current
research
demonstrated
that
implicated
SARS-CoV-2
infection,
although
opposing
conclusions
have
been
drawn
studies.
Here,
we
review
knowledge
on
molecular
actions
under
both
healthy
diseased
settings,
well
its
functional
effects
targets.
Finally,
revise
potential
therapeutic
target
provide
overview
currently
reported
modulators,
which
include
activators
inhibitors.
Signal Transduction and Targeted Therapy,
Journal Year:
2019,
Volume and Issue:
4(1)
Published: Dec. 17, 2019
Epigenetic
alternations
concern
heritable
yet
reversible
changes
in
histone
or
DNA
modifications
that
regulate
gene
activity
beyond
the
underlying
sequence.
dysregulation
is
often
linked
to
human
disease,
notably
cancer.
With
development
of
various
drugs
targeting
epigenetic
regulators,
epigenetic-targeted
therapy
has
been
applied
treatment
hematological
malignancies
and
exhibited
viable
therapeutic
potential
for
solid
tumors
preclinical
clinical
trials.
In
this
review,
we
summarize
aberrant
functions
enzymes
methylation,
acetylation
methylation
during
tumor
progression
highlight
inhibitors
targeted
at
enzymes.
Antioxidants and Redox Signaling,
Journal Year:
2017,
Volume and Issue:
28(8), P. 643 - 661
Published: Sept. 11, 2017
Antioxidant
and
redox
signaling
(ARS)
events
are
regulated
by
critical
molecules
that
modulate
antioxidants,
reactive
oxygen
species
(ROS)
or
nitrogen
(RNS),
and/or
oxidative
stress
within
the
cell.
Imbalances
in
these
can
disturb
cellular
functions
to
become
pathogenic.
Sirtuins
serve
as
important
regulators
of
ARS
cells.
Recent
Advances:
(SIRTs
1-7)
a
family
nicotinamide
adenine
dinucleotide
(NAD)-dependent
histone
deacetylases
with
ability
deacetylate
nonhistone
targets.
studies
show
sirtuins
regulation
variety
processes
associated
ARS.
SIRT1,
SIRT3,
SIRT5
protect
cell
from
ROS,
SIRT2,
SIRT6,
SIRT7
key
genes
mechanisms.
Interestingly,
SIRT4
has
been
shown
induce
ROS
production
antioxidative
roles
well.A
complete
understanding
homeostasis
is
very
understand
normal
functioning
well
pathological
manifestations.
In
this
review,
we
have
provided
discussion
on
role
We
also
discussed
mechanistic
interactions
among
different
sirtuins.
Indeed,
sirtuin
biology
could
be
at
multiple
fronts.Sirtuins
emerging
mammalian
physiology
stress-mediated
situations.
Studies
needed
dissect
mechanisms
maintaining
homeostasis.
Efforts
required
assess
targetability
management
redox-regulated
diseases.
Antioxid.
Redox
Signal.
28,
643-661.
Clinical Epigenetics,
Journal Year:
2016,
Volume and Issue:
8(1)
Published: May 24, 2016
Sirtuins
are
NAD+-dependent
histone
deacetylases
regulating
important
metabolic
pathways
in
prokaryotes
and
eukaryotes
involved
many
biological
processes
such
as
cell
survival,
senescence,
proliferation,
apoptosis,
DNA
repair,
metabolism,
caloric
restriction.
The
seven
members
of
this
family
enzymes
considered
potential
targets
for
the
treatment
human
pathologies
including
neurodegenerative
diseases,
cardiovascular
cancer.
Furthermore,
recent
interest
focusing
on
sirtuin
modulators
epigenetic
players
regulation
fundamental
has
prompted
increased
efforts
to
discover
new
small
molecules
able
modify
activity.
Here,
we
review
role,
mechanism
action,
function
sirtuins,
well
their
inhibitors
activators.
Critical Reviews in Biochemistry and Molecular Biology,
Journal Year:
2018,
Volume and Issue:
53(3), P. 311 - 334
Published: April 11, 2018
Sirtuins
are
NAD+-dependent
protein
deacylases/ADP-ribosyltransferases
that
have
emerged
as
candidate
targets
for
new
therapeutics
to
treat
metabolic
disorders
and
other
diseases,
including
cancer.
The
sirtuin
SIRT5
resides
primarily
in
the
mitochondrial
matrix
catalyzes
removal
of
negatively
charged
lysine
acyl
modifications;
succinyl,
malonyl,
glutaryl
groups.
Evidence
has
now
accumulated
document
roles
a
significant
regulator
cellular
homeostasis,
context-
cell-type
specific
manner,
been
observed
previously
family
members.
regulates
substrates
involved
glycolysis,
TCA
cycle,
fatty
acid
oxidation,
electron
transport
chain,
ketone
body
formation,
nitrogenous
waste
management,
ROS
detoxification,
among
processes.
plays
pivotal
cardiac
physiology
stress
responses
is
regulation
numerous
aspects
myocardial
energy
metabolism.
implicated
neoplasia,
both
tumor
promoter
suppressor
context-specific
may
serve
protective
function
setting
neurodegenerative
disorders.
Here,
we
review
current
understanding
functional
impacts
on
its
targets,
molecular
functions
normal
pathological
conditions.
Finally,
will
discuss
potential
utility
drug
target
also
summarize
status,
progress,
challenges
developing
small
molecule
compounds
modulate
activity
with
high
potency
specificity.
Frontiers in Pharmacology,
Journal Year:
2019,
Volume and Issue:
10
Published: Jan. 29, 2019
Sirtuins,
class
III
histone
deacetylases,
are
differentially
expressed
in
several
human
cancers,
where
they
display
both
oncogenic
and
tumor-suppressive
properties
depending
on
cellular
context
experimental
conditions.
Sirtuins
involved
many
important
biological
processes
play
a
critical
role
cancer
initiation,
promotion
progression.
A
growing
body
of
evidence
indicates
the
involvement
sirtuins
regulating
three
tumor
processes:
epithelial-to-mesenchymal
transition
(EMT),
invasion
metastasis.
Many
responsible
for
metabolic
reprogramming
drug
resistance
by
inactivating
cell
death
pathways
promoting
uncontrolled
proliferation.
In
this
review,
we
summarize
current
knowledge
discuss
their
puzzling
dual
function
as
suppressors
promoters,
future
development
novel
tailored
sirtuin-based
therapies.