Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 944 - 944
Опубликована: Янв. 23, 2025
Mitochondria
serve
an
essential
metabolic
and
energetic
role
in
cellular
activity,
their
dysfunction
has
been
implicated
a
wide
range
of
disorders,
including
cardiovascular
conditions,
neurodegenerative
syndromes.
Mitochondria-targeted
therapies,
such
as
Elamipretide
(SS-31,
MTP-131,
Bendavia),
have
consequently
emerged
topic
scientific
clinical
interest.
unique
structure
allowing
for
uptake
variety
cell
types
highly
selective
mitochondrial
targeting.
This
mitochondria-targeting
tetrapeptide
selectively
binds
cardiolipin
(CL),
lipid
found
the
inner
membrane,
thus
stabilizing
cristae
structure,
reducing
oxidative
stress,
enhancing
adenosine
triphosphate
(ATP)
production.
Preclinical
studies
demonstrated
protective
restorative
efficacy
models
heart
failure,
neurodegeneration,
ischemia–reperfusion
injury,
syndromes,
muscle
atrophy
weakness.
Clinical
trials
PROGRESS-HF,
TAZPOWER,
MMPOWER-3,
ReCLAIM
elaborate
on
preclinical
findings
highlight
significant
therapeutic
potential
Elamipretide.
Further
research
may
expand
its
application
to
other
diseases
involving
well
investigate
long-term
safety
drug.
The
following
review
synthesizes
current
knowledge
mechanisms
action,
promising
fitness,
improving
bioenergetics,
minimizing
stress.
Язык: Английский
A look at MERCs as UPRmt regulatory hubs in age-associated heart diseases
The Journal of Cardiovascular Aging,
Год журнала:
2025,
Номер
5(1)
Опубликована: Янв. 22, 2025
With
the
increase
in
life
expectancy
globally,
challenge
of
dealing
with
aging
becomes
more
prominent.
Aging
is
a
risk
factor
for
several
diseases,
including
cardiovascular
disease.
Mitochondria,
which
have
long
been
studied
relation
to
aging,
play
crucial
role
maintaining
cellular
homeostasis.
However,
there
limitation
interorganellar
communication
as
organisms
age.
The
unfolded
protein
response
mitochondria
(UPRmt)
activated
during
stress
maintain
mitochondrial
homeostasis
and
prevent
accumulation
damaged
mitochondria.
This
involves
signaling
from
nucleus,
leading
transcriptional
changes.
In
context
heart,
this
review
explores
terms
function
morphology.
It
also
discusses
impact
UPRmt
on
cardiac
diseases
such
heart
failure,
acute
myocardial
infarction,
dilated
cardiomyopathy.
highlights
potential
mitochondria-endoplasmic
reticulum
contact
sites
(MERCs)
modulating
aging.
Finally,
it
provides
an
update
molecules
that
induce
activity,
potentially
benefiting
Язык: Английский
Mitochondrial Electron Transport Chain Disruption and Oxidative Stress in Lipopolysaccharide-Induced Cardiac Dysfunction in rats and mice
Free Radical Research,
Год журнала:
2025,
Номер
unknown, С. 1 - 14
Опубликована: Май 8, 2025
Sepsis,
characterized
by
severe
systemic
inflammation
and
an
excessive
immune
response
to
infection,
is
frequently
triggered
bacterial
endotoxins
like
lipopolysaccharide
(LPS)
from
Gram-negative
bacteria.
Moreover,
sepsis-induced
cardiac
dysfunction
remains
a
leading
cause
of
mortality.
This
study
aims
elucidate
the
effects
LPS-induced
injury
on
mitochondrial
damage,
oxidative
stress,
subsequent
dysfunction.
LPS
injections
(in
rats
mice)
for
three
days
(1.5
mg/kg)
impacted
body
weight
increased
TNF-α.
Additionally,
it
decreased
complexes
I
II
activities
while
III
IV
remained
unaffected.
Disturbed
in
electron
transport
chain
leads
increase
reactive
oxygen
species
(ROS).
Indeed,
treatment
significantly
hydrogen
peroxide
production,
reduced
activity
antioxidant
enzymes
catalase,
superoxide
dismutase,
glutathione
peroxidase,
reductase
activity.
was
accompanied
cytosolic
sulfhydryl
proteins
parallel
cellular
lipid
peroxidation
presence
or
absence
Fe2+.
LPS-treated
samples
had
s-transferase
activity,
which
may
be
attempt
cell
remove
toxic
products.
In
more
acute
Langendorff-perfused
rat
hearts,
infusion
(0.5
μg/mL)
induced
significant
elevation
left
ventricular
end-diastolic
pressure
decrease
developed
pressure.
These
findings
harmful
tissue
could
help
development
targeted
therapies
mitigate
adverse
Язык: Английский
Aging and rejuvenation of engineered cardiovascular tissues: from research to clinical application
The Journal of Cardiovascular Aging,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 14, 2024
Aging
is
a
key
contributor
to
the
pathogenesis
of
cardiovascular
diseases
(CVDs).
However,
current
methods
and
models
CVD
do
not
include
factor
aging
due
use
premature
cardiomyocytes.
There
an
urgent
need
for
engineered
tissue
(ECT)
model
that
includes
as
greatest
risk
facilitate
drug
development
aged
patients.
Cell
therapy,
which
transplants
pluripotent
stem
cell-derived
cardiomyocytes
in
patients,
was
proved
be
effective
cardiac
repair,
while
cell
retention
rate
limited.
Alternatively,
implantation
ECT
could
enable
long-term
cells
after
translation
may
result
rejuvenation
hearts.
This
review
summarizes
features
influencing
factors
tissues.
The
applications
challenges
myocardium
designed
clinical
are
also
discussed.
Язык: Английский
High Dose Metformin Treatment to Inhibit Complex I during Early Reperfusion Protects the Aged Mouse Heart via Decreased MPTP Opening
Journal of Pharmacology and Experimental Therapeutics,
Год журнала:
2024,
Номер
392(3), С. 100529 - 100529
Опубликована: Дек. 24, 2024
Acute,
high-dose
metformin
(MET,
2
mM)
results
in
partial
complex
I
inhibition
ischemia
(ISC)-modified
mitochondria.
Mitochondrial
permeability
transition
pore
(MPTP)
opening
increases
cardiac
injury
during
ISC-reperfusion
(REP).
We
evaluated
whether
MET
(2
can
decrease
MPTP
aged
hearts
REP.
Sestrin2
(Sesn2)
regulates
metabolism
through
activation
of
AMP-dependent
protein
kinase.
Sesn2
decreases
hearts.
The
knockout
(KO)
mimics
the
aging
phenotype.
Inactivation
glycogen
synthase
kinase-3
β
(GSK-3β)
via
serine-9
phosphorylation
opening.
assessed
if
mM
given
early
REP
by
blockade
with
decreased
and
protection
depends
on
Sesn2-mediated
GSK-3β
phosphorylation.
C57BL/6BJ
male
mice
(22-24
months)
adult
KO
were
evaluated.
dose-dependently
inhibited
NADH
oxidase
activity
permeabilized
mitochondria
both
greater
after
25
minutes
ISC.
infarct
size
improved
calcium
retention
capacity
wild-type
mice.
treatment
only
increased
heart
but
not
Thus,
at
partially
inhibits
susceptibility
downstream
is
fully
dependent
inhibition.
Complex
downregulation
acute,
has
translational
potential
to
protect
heart.
SIGNIFICANCE
STATEMENT:
This
study
explores
efficacy
mechanism
acute
reducing
mitochondrial-driven
reperfusion
stop-flow
high-risk
Metformin
(NADH
oxidation)
ischemia-altered
mitigated
as
injury.
modulation
application
mitigate
ST-elevation
myocardial
infarction
Язык: Английский