Chemical Biology & Drug Design,
Journal Year:
2025,
Volume and Issue:
105(4)
Published: April 1, 2025
Sirtuins,
a
class
of
NAD+
-dependent
deacetylases,
play
key
role
in
aging,
metabolism,
and
longevity.
Their
interaction
with
at
the
catalytic
site
is
crucial
for
function,
but
experimental
methods
to
map
binding
sites
are
time
consuming.
To
address
this,
we
developed
computational
method
integrating
pretrained
protein
language
models
multiwindow
convolutional
neural
networks
(CNNs).
This
captures
sequence
information
diverse
local
patterns,
achieving
state-of-the-art
performance,
AUC
0.9733
human
sirtuin
proteins
0.9701
other
NAD-dependent
deacylation
enzymes.
These
findings
offer
insights
into
sirtuins
aging
their
broader
biological
functions
while
providing
new
path
identifying
therapeutic
targets
aging-related
diseases.
EBioMedicine,
Journal Year:
2023,
Volume and Issue:
98, P. 104863 - 104863
Published: Nov. 9, 2023
BackgroundTherapies
are
urgently
required
to
ameliorate
pathological
cardiac
hypertrophy
and
enhance
function
in
heart
failure.
Our
preliminary
experiments
have
demonstrated
that
exogenous
NADPH
exhibits
a
positive
inotropic
effect
on
isolated
heart.
This
study
aims
investigate
the
effects
of
failure,
as
well
underlying
mechanisms
involved.MethodsEndogenous
plasma
contents
were
determined
patients
with
chronic
failure
control
adults.
The
investigated
toad
or
rat
isoproterenol
(ISO)–induced
transverse
aortic
constriction
(TAC)–induced
studied
using
SIRT3
knockout
mice,
echocardiography,
Western
blotting,
transmission
electron
microscopy,
immunoprecipitation.FindingsThe
endogenous
content
blood
animals
was
significantly
reduced
compared
age-sex
matched
subjects.
Exogenous
showed
normal
failing
hearts,
while
antagonism
ATP
receptor
partially
abolished
NADPH.
administration
weight
indices,
improved
mice
increased
expression
activity,
deacetylated
target
proteins,
mitochondrial
facilitated
production
hypertrophic
myocardium.
Importantly,
inhibition
NADPH,
anti-heart
Knockout
mice.InterpretationExogenous
shows
improves
energy
metabolism
via
thus
may
be
one
potential
candidates
for
treatment
failure.FundingThis
work
supported
by
grants
from
National
Natural
Science
Foundation
China
(No.
81973315,
82173811,
81730092),
Jiangsu
Higher
Education
(20KJA310008),
Key
Laboratory
Neuropsychiatric
Diseases
(BM2013003)
Priority
Academic
Program
Development
Institutes
(PAPD).
Biomedicine & Pharmacotherapy,
Journal Year:
2023,
Volume and Issue:
170, P. 116004 - 116004
Published: Dec. 11, 2023
Dysregulation
of
mitochondrial
homeostasis
is
common
to
all
types
cardiovascular
diseases.
SIRT3
regulates
apoptosis
and
autophagy,
material
energy
metabolism,
oxidative
stress,
inflammation,
fibrosis.
As
an
important
mediator
node
in
the
network
mechanisms,
essential
many
activities.
This
review
explains
how
tricarboxylic
acid
cycle
treat
A
novel
description
impact
lifestyle
factors
on
expression
from
angles
nutrition,
exercise,
temperature
provided.
Free Radical Biology and Medicine,
Journal Year:
2022,
Volume and Issue:
195, P. 270 - 282
Published: Dec. 31, 2022
The
metabolic
patterns
and
energetics
of
human
induced
pluripotent
stem
cell-derived
cardiomyocytes
(HiPSC-CMs)
are
much
less
than
those
normal
adult
cardiomyocytes,
which
has
limited
their
application
in
disease
therapy
regenerative
medicine.
It
been
demonstrated
that
SIRT3,
a
mitochondria-target
deacetylase,
controls
mitochondrial
metabolism
physiological
pathological
conditions.
In
this
research,
We
investigated
the
role
regulatory
mechanism
SIRT3
energy
HiPSC-CMs.
found
expression
was
increased
during
differentiation
maturation
Knocking
down
impaired
structure,
respiration
capacity,
fatty
acid
oxidation
but
enhanced
glycolysis.
However,
honokiol,
pharmacological
activator
improved
ultrastructure
energetics,
promoted
oxidative
phosphorylation
Furthermore,
regulated
acetylation
OPA1,
knockdown
OPA1
blocked
promotion
by
meanwhile,
knocking
fusion,
were
reversed
M1
(a
fusion
promoter)
summary,
remodeling
targeting
OPA1-controlled
dynamics
HiPSC-CMs,
may
have
revelatory
implications
treatment
cardiovascular
diseases
HiPSC-CMs
to
Circulation,
Journal Year:
2023,
Volume and Issue:
149(14), P. 1102 - 1120
Published: Dec. 21, 2023
Diabetes
is
associated
with
cardiovascular
complications.
microRNAs
translocate
into
subcellular
organelles
to
modify
genes
involved
in
diabetic
cardiomyopathy.
However,
functional
properties
of
AGO2
(Argonaute2),
a
core
member
miRNA
machinery,
remain
elusive.
Pharmacological Research,
Journal Year:
2024,
Volume and Issue:
207, P. 107324 - 107324
Published: July 24, 2024
This
review
rigorously
assesses
the
burgeoning
research
into
role
of
polyphenols
in
modulating
mitophagy,
an
essential
cellular
mechanism
for
targeted
removal
impaired
mitochondria.
These
natural
compounds,
known
their
low
toxicity,
are
underscored
potential
therapeutic
strategies
against
a
diverse
array
diseases,
such
as
neurodegenerative,
cardiovascular,
and
musculoskeletal
disorders.
The
analysis
penetrates
deeply
molecular
mechanisms
whereby
promote
particularly
by
influencing
crucial
signaling
pathways
transcriptional
regulators,
including
phosphatase
tensin
homolog
(PTEN)
induced
putative
kinase
1
(PINK1)/parkin
forkhead
box
O3
(FOXO3a)
pathways.
Noteworthy
discoveries
include
neuroprotective
properties
resveratrol
curcumin,
which
affect
both
autophagic
mitochondrial
dynamics,
pioneering
integration
with
other
substances
to
amplify
effectiveness.
Furthermore,
confronts
issue
polyphenol
bioavailability
emphasizes
imperative
clinical
trials
corroborate
viability.
By
delivering
exhaustive
synthesis
contemporary
insights
recent
advancements
mitophagy
research,
this
endeavors
catalyze
additional
foster
creation
innovative
modalities
that
exploit
distinctive
attributes
manage
prevent
disease.
