Current Opinion in Neurology,
Journal Year:
2024,
Volume and Issue:
38(1), P. 79 - 86
Published: Dec. 20, 2024
Purpose
of
review
Leber
hereditary
optic
neuropathy
(LHON)
is
a
mitochondrial
DNA
disease
characterised
by
sequential
bilateral
vision
loss
due
to
retinal
ganglion
cells.
The
purpose
this
provide
an
update
on
the
results
recent
clinical
trials
for
LHON,
focusing
studies
idebenone
and
lenadogene
nolparvovec
gene
therapy.
Recent
findings
Evidence
from
three
(RHODOS,
RHODOS-OFU,
LEROS)
suggest
that
should
be
started
early
continued
at
least
24
months.
Treatment
effect
varies
according
stage
LHON
underlying
mutation.
Favourable
outcomes
are
associated
with
m.11778G>A
mutation
chronic
eyes
m.14484T>C
Caution
taken
in
subacute/dynamic
m.3460G>A
mutation,
possible
worsening
idebenone.
Compared
external
natural
history
cohort,
pooled
data
four
(RESCUE,
REVERSE,
RESTORE
REFLECT)
show
single
intravitreal
injection
can
result
sustained
visual
improvement
patients
aged
≥15
years
when
treated
within
1
year
onset.
Although
treatment
modest,
final
acuity
(∼1.2
logMAR)
significantly
differs
published
benefit
more
pronounced
than
alone
Summary
There
increasing
evidence
potential
therapeutic
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: Jan. 9, 2025
Abstract
Mitochondria
are
essential
for
cellular
function
and
viability,
serving
as
central
hubs
of
metabolism
signaling.
They
possess
various
metabolic
quality
control
mechanisms
crucial
maintaining
normal
activities.
Mitochondrial
genetic
disorders
can
arise
from
a
wide
range
mutations
in
either
mitochondrial
or
nuclear
DNA,
which
encode
proteins
other
contents.
These
defects
lead
to
breakdown
metabolism,
such
the
collapse
oxidative
phosphorylation,
one
mitochondria’s
most
critical
functions.
diseases,
common
group
disorders,
characterized
by
significant
phenotypic
heterogeneity.
Clinical
symptoms
manifest
systems
organs
throughout
body,
with
differing
degrees
forms
severity.
The
complexity
relationship
between
mitochondria
diseases
results
an
inadequate
understanding
genotype-phenotype
correlation
these
historically
making
diagnosis
treatment
challenging
often
leading
unsatisfactory
clinical
outcomes.
However,
recent
advancements
research
technology
have
significantly
improved
our
management
conditions.
translations
mitochondria-related
therapies
actively
progressing.
This
review
focuses
on
physiological
mitochondria,
pathogenesis
potential
diagnostic
therapeutic
applications.
Additionally,
this
discusses
future
perspectives
diseases.
Free Radical Biology and Medicine,
Journal Year:
2024,
Volume and Issue:
222, P. 211 - 222
Published: June 20, 2024
Oxygen
is
essential
for
aerobic
life
on
earth
but
it
also
the
origin
of
harmful
reactive
oxygen
species
(ROS).
Ubiquinone
par
excellence
endogenous
cellular
antioxidant,
a
very
hydrophobic
one.
Because
that,
other
molecules
have
been
envisaged,
such
as
idebenone
(IDE)
and
mitoquinone
(MTQ),
having
same
redox
active
benzoquinone
moiety
higher
solubility.
We
used
molecular
dynamics
to
determine
location
interaction
these
molecules,
both
in
their
oxidized
reduced
forms,
with
membrane
lipids
similar
that
mitochondria.
Both
IDE
(IDOL)
are
situated
near
interface,
whereas
MTQ
(MTQOL)
locate
position
adjacent
phospholipid
hydrocarbon
chains.
The
quinone
moieties
ubiquinone
10
(UQ10)
UQ10
(UQOL10)
contraposition
IDE,
IDOL,
MTQOL,
located
interphase,
isoprenoid
chains
remained
at
middle
These
do
not
aggregate
functional
different
depths
whereby
protecting
them
from
ROS
effects.
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 26, 2025
Drug
resistance
is
a
prevalent
challenge
in
clinical
disease
treatment,
often
leading
to
relapse
and
poor
prognosis.
Therefore,
it
crucial
gain
deeper
understanding
of
the
molecular
mechanisms
underlying
drug
develop
targeted
strategies
for
its
effective
prevention
management.
Mitochondria,
as
vital
energy-producing
organelles
within
cells,
have
been
recognized
key
regulators
sensitivity.
Processes
such
mitochondrial
fission,
fusion,
mitophagy,
changes
membrane
potential,
reactive
oxygen
species
(ROS)
accumulation,
oxidative
phosphorylation
(OXPHOS)
are
all
linked
Non-coding
RNAs
(ncRNAs)
enriched
mitochondria
(mtncRNA),
whether
transcribed
from
DNA
(mtDNA)
or
nucleus
transported
mitochondria,
can
regulate
transcription
translation
mtDNA,
thus
influencing
function,
including
substance
exchange
energy
metabolism.
This,
turn,
directly
indirectly
affects
cellular
sensitivity
drugs.
This
review
summarizes
types
mtncRNAs
associated
with
regulating
resistance.
Our
aim
provide
insights
overcoming
by
modulating
mtncRNAs.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(16), P. 8626 - 8626
Published: Aug. 7, 2024
This
review
explored
the
role
of
mitochondria
in
retinal
ganglion
cells
(RGCs),
which
are
essential
for
visual
processing.
Mitochondrial
dysfunction
is
a
key
factor
pathogenesis
various
vision-related
disorders,
including
glaucoma,
hereditary
optic
neuropathy,
and
age-related
macular
degeneration.
highlighted
critical
RGCs,
provide
metabolic
support,
regulate
cellular
health,
respond
to
stress
while
also
producing
reactive
oxygen
species
(ROS)
that
can
damage
components.
Maintaining
mitochondrial
function
meeting
RGCs’
high
demands
ensuring
redox
homeostasis,
crucial
their
proper
health.
Oxidative
stress,
exacerbated
by
factors
like
elevated
intraocular
pressure
environmental
factors,
contributes
diseases
such
as
glaucoma
vision
loss
triggering
pathways.
Strategies
targeting
or
bolstering
antioxidant
defenses
include
mitochondrial-based
therapies,
gene
transplantation.
These
advances
offer
potential
strategies
addressing
retina,
with
implications
extend
beyond
ocular
diseases.
Expert Opinion on Biological Therapy,
Journal Year:
2024,
Volume and Issue:
24(6), P. 521 - 528
Published: June 2, 2024
Introduction
Leber
hereditary
optic
neuropathy
(LHON)
is
among
the
most
frequent
inherited
mitochondrial
disease,
causing
a
severe
visual
impairment,
mostly
in
young-adult
males.
The
causative
mtDNA
variants
(the
three
common
are
m.11778
G>A/MT-ND4,
m.3460
G>A/MT-ND1,
and
m.14484T>C/MT-ND6)
by
affecting
complex
I
impair
oxidative
phosphorylation
retinal
ganglion
cells,
ultimately
leading
to
irreversible
cell
death
consequent
functional
loss.
gene
therapy
based
on
allotopic
expression
of
wild-type
transgene
carried
adeno-associated
viral
vectors
(AVV-based)
appears
promising
approach
disease
its
efficacy
has
been
explored
several
large
clinical
trials.
Journal of Clinical & Translational Ophthalmology,
Journal Year:
2024,
Volume and Issue:
2(3), P. 64 - 78
Published: June 26, 2024
Hereditary
optic
neuropathies
(HONs)
are
a
class
of
genetic
disorders
that
may
lead
to
vision
loss
due
either
acute
or
progressive
injury
the
nerve.
Although
HONs
commonly
manifest
as
isolated
atrophy,
these
can
also
have
variety
characteristic
clinical
features
and
time
courses
narrow
differential
diagnosis.
While
two
most
prevalent
Leber
Optic
Neuropathy
(LHON)
Dominant
Atrophy
(DOA),
phenotypic
spectrum
conditions,
well
landscape
less
common
neuropathies,
been
better
characterized
through
advances
in
molecular
diagnostic
testing.
Treatment
targeting
various
pathogenic
mechanisms
has
investigated,
although
studies
applicability
remain
nascent.
Present
management
largely
remains
supportive.
In
this
review,
we
discuss
features,
diagnosis,
current
treatment,
future
directions
for
HONs.
