Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(14), С. 7952 - 7952
Опубликована: Июль 21, 2024
Alzheimer's
disease
(AD)
and
Parkinson's
(PD)
are
the
most
common
neurodegenerative
diseases,
they
affect
millions
of
people
worldwide,
particularly
older
individuals.
Therefore,
there
is
a
clear
need
to
develop
novel
drug
targets
for
treatment
age-related
diseases.
Emerging
evidence
suggests
that
mitochondrial
dysfunction
reactive
oxygen
species
(ROS)
generation
play
central
roles
in
onset
progression
Mitochondria
key
regulators
respiratory
function,
cellular
energy
adenosine
triphosphate
production,
maintenance
redox
homeostasis,
which
essential
cell
survival.
Mitochondrial
morphology
function
tightly
regulated
by
maintaining
balance
among
fission,
fusion,
biogenesis,
mitophagy.
In
this
review,
we
provide
an
overview
main
functions
mitochondria,
with
focus
on
recent
progress
highlighting
critical
role
ROS-induced
oxidative
stress,
dysregulated
dynamics,
apoptosis,
mitochondria-associated
inflammation,
impaired
pathogenesis
such
as
AD
PD.
We
also
discuss
potential
fusion
biogenesis
enhancers,
fission
inhibitors,
mitochondria-targeted
antioxidants
drugs
these
Язык: Английский
Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies
Neurotherapeutics,
Год журнала:
2025,
Номер
unknown, С. e00525 - e00525
Опубликована: Янв. 1, 2025
Язык: Английский
Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Фев. 7, 2025
Mitochondrial
dysfunction
is
a
pivotal
instigator
of
neuroinflammation,
with
mitochondrial
DNA
(mtDNA)
leakage
as
critical
intermediary.
This
review
delineates
the
intricate
pathways
leading
to
mtDNA
release,
which
include
membrane
permeabilization,
vesicular
trafficking,
disruption
homeostatic
regulation,
and
abnormalities
in
dynamics.
The
escaped
activates
cytosolic
sensors,
especially
cyclic
gmp-amp
synthase
(cGAS)
signalling
inflammasome,
initiating
neuroinflammatory
cascades
via
pathways,
exacerbating
spectrum
neurological
pathologies.
therapeutic
promise
targeting
discussed
detail,
underscoring
necessity
for
multifaceted
strategy
that
encompasses
preservation
homeostasis,
prevention
leakage,
reestablishment
dynamics,
inhibition
activation
sensors.
Advancing
our
understanding
complex
interplay
between
neuroinflammation
imperative
developing
precision
interventions
disorders.
Язык: Английский
Role of dynamin-related protein 1-dependent mitochondrial fission in drug-induced toxicity
Pharmacological Research,
Год журнала:
2024,
Номер
206, С. 107250 - 107250
Опубликована: Июнь 13, 2024
Dynamin-related
protein
1
(DRP1)
is
an
essential
controller
of
mitochondrial
fission
whose
activity
tightly
controlled
to
ensure
balanced
dynamics
and
maintain
internal
cellular
homeostasis.
Growing
evidence
suggests
that
DRP1-dependent
plays
a
role
in
drug-induced
toxicity
(DIT).
Therefore,
understanding
the
molecular
mechanisms
underlying
DIT
precise
regulation
DRP1
function
will
inform
development
potential
therapeutic
treatments
for
DIT.
This
review
comprehensively
summarizes
diverse
DITs
their
mechanism
associated
with
discusses
vivo
vitro
model
studies
protection
targeting
DRP1.
Язык: Английский
Nuclear respiratory factor-1 (NRF1) induction drives mitochondrial biogenesis and attenuates amyloid beta-induced mitochondrial dysfunction and neurotoxicity
Neurotherapeutics,
Год журнала:
2024,
Номер
unknown, С. e00513 - e00513
Опубликована: Дек. 1, 2024
Язык: Английский
Nilotinib as a Prospective Treatment for Alzheimer’s Disease: Effect on Proteins Involved in Neurodegeneration and Neuronal Homeostasis
Life,
Год журнала:
2024,
Номер
14(10), С. 1241 - 1241
Опубликована: Сен. 28, 2024
Nilotinib,
a
tyrosine
kinase
inhibitor
that
targets
the
Abelson
(c-Abl)
signaling
pathway,
is
FDA-approved
to
treat
chronic
myeloid
leukemia.
Nilotinib
has
properties
indicative
of
possible
utility
in
neuroprotection
have
prompted
exploration
repurposing
drug
for
treatment
Alzheimer's
disease
(AD)
and
Parkinson's
(PD).
AD
progressive
age-related
neurodegenerative
disorder
characterized
by
deposition
extracellular
amyloid-β
plaques
intracellular
neurofibrillary
tangles.
It
incurable
affects
approximately
50
million
patients
worldwide.
reduces
c-Abl
phosphorylation,
levels,
dopaminergic
neuron
degeneration
preclinical
models.
This
study
explores
effects
nilotinib
on
amyloid
processing
mitochondrial
functioning
SH-SY5Y
human
neuroblastoma
cell
line.
cells
were
exposed
(1,
5,
10
µM).
Real-time
PCR
immunoblot
analysis
performed
quantify
expression
genes
pertaining
neuronal
health.
did
not
significantly
change
APP,
BACE1,
or
ADAM10
mRNA
levels.
However,
BACE1
protein
was
increased
at
1
µM,
µM
without
affecting
APP
expression.
Further,
affect
associated
with
health
functioning.
Taken
together,
our
findings
do
support
efficacy
neuroprotection.
Язык: Английский