International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(23), С. 17027 - 17027
Опубликована: Дек. 1, 2023
Mitochondrial
dysregulation,
such
as
mitochondrial
complex
I
deficiency,
increased
oxidative
stress,
perturbation
of
dynamics
and
mitophagy,
has
long
been
implicated
in
the
pathogenesis
PD.
Initiating
from
observation
that
toxins
cause
PD-like
symptoms
DNA
mutations
are
associated
with
risk
PD,
many
mutated
genes
linked
to
familial
forms
including
PRKN,
PINK1,
DJ-1
SNCA,
have
also
found
affect
features.
Recent
research
uncovered
a
much
more
involvement
mitochondria
Disruption
quality
control
coupled
abnormal
secretion
contents
dispose
damaged
organelles
may
play
role
Furthermore,
due
its
bacterial
ancestry,
circulating
DNAs
can
function
damage-associated
molecular
patterns
eliciting
inflammatory
response.
In
this
review,
we
summarize
discuss
connection
between
dysfunction
highlighting
triggers
disease
process,
intra-
extracellular
roles
PD
well
therapeutic
potential
transplantation.
Genes,
Год журнала:
2022,
Номер
13(3), С. 471 - 471
Опубликована: Март 7, 2022
Parkinson’s
disease
may
be
caused
by
a
single
pathogenic
variant
(monogenic)
in
5–10%
of
cases,
but
investigation
these
disorders
provides
valuable
pathophysiological
insights.
In
this
review,
we
discuss
each
genetic
form
with
focus
on
genotype,
phenotype,
pathophysiology,
and
the
geographic
ethnic
distribution.
Well-established
genes
include
autosomal
dominant
forms
(SNCA,
LRRK2,
VPS35)
recessive
(PRKN,
PINK1
DJ1).
Furthermore,
mutations
GBA
gene
are
key
risk
factor
for
disease,
there
have
been
major
developments
X-linked
dystonia
parkinsonism.
Moreover,
atypical
or
complex
parkinsonism
due
to
such
as
ATP13A2,
DCTN1,
DNAJC6,
FBXO7,
PLA2G6,
SYNJ1.
numerous
recently
implicated
CHCHD2,
LRP10,
TMEM230,
UQCRC1,
VPS13C.
Additionally,
role
heterozygous
genes,
effect
having
two
outcome
deep
brain
stimulation,
testing.
We
highlight
that
monogenic
is
influenced
ethnicity
geographical
differences,
reinforcing
need
global
efforts
pool
large
numbers
patients
identify
novel
candidate
genes.
Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Ноя. 11, 2023
Abstract
Mitochondrial
dysfunction
is
strongly
implicated
in
the
etiology
of
idiopathic
and
genetic
Parkinson’s
disease
(PD).
However,
strategies
aimed
at
ameliorating
mitochondrial
dysfunction,
including
antioxidants,
antidiabetic
drugs,
iron
chelators,
have
failed
disease-modification
clinical
trials.
In
this
review,
we
summarize
cellular
determinants
impairment
electron
transport
chain
complex
1,
increased
oxidative
stress,
disturbed
quality
control
mechanisms,
bioenergetic
deficiency.
addition,
outline
pathways
to
neurodegeneration
current
context
PD
pathogenesis,
review
past
treatment
an
attempt
better
understand
why
translational
efforts
thus
far
been
unsuccessful.
Journal of Biomedical Science,
Год журнала:
2023,
Номер
30(1)
Опубликована: Окт. 12, 2023
Mitochondrial
mass
and
quality
are
tightly
regulated
by
two
essential
opposing
mechanisms,
mitochondrial
biogenesis
(mitobiogenesis)
mitophagy,
in
response
to
cellular
energy
needs
other
environmental
cues.
Great
strides
have
been
made
uncover
key
regulators
of
these
complex
processes.
Emerging
evidence
has
shown
that
there
exists
a
tight
coordination
between
mitophagy
mitobiogenesis,
their
defects
may
cause
many
human
diseases.
In
this
review,
we
will
first
summarize
the
recent
advances
discovery
molecular
regulations
mitobiogenesis
then
focus
on
mechanism
signaling
pathways
involved
simultaneous
regulation
tissue
or
cultured
cells
needs,
stress,
pathophysiological
conditions.
Further
studies
crosstalk
processes
at
level
provide
better
understanding
how
cell
maintains
optimal
fitness
function
under
physiological
conditions,
which
holds
promise
for
fighting
aging
aging-related
Biomedicines,
Год журнала:
2023,
Номер
11(9), С. 2488 - 2488
Опубликована: Сен. 7, 2023
Mitochondria
play
a
vital
role
in
maintaining
cellular
energy
homeostasis,
regulating
apoptosis,
and
controlling
redox
signaling.
Dysfunction
of
mitochondria
has
been
implicated
the
pathogenesis
various
brain
diseases,
including
neurodegenerative
disorders,
stroke,
psychiatric
illnesses.
This
review
paper
provides
comprehensive
overview
intricate
relationship
between
disease,
focusing
on
underlying
pathological
mechanisms
exploring
potential
therapeutic
opportunities.
The
covers
key
topics
such
as
mitochondrial
DNA
mutations,
impaired
oxidative
phosphorylation,
dynamics,
calcium
dysregulation,
reactive
oxygen
species
generation
context
disease.
Additionally,
it
discusses
emerging
strategies
targeting
dysfunction,
protective
agents,
metabolic
modulators,
gene
therapy
approaches.
By
critically
analysing
existing
literature
recent
advancements,
this
aims
to
enhance
our
understanding
multifaceted
disease
shed
light
novel
interventions.
Abstract
Mitochondrial
dysfunction
of
neurons
is
the
core
pathogenesis
incurable
Parkinson's
disease
(PD).
It
crucial
to
ameliorate
mitochondrial
for
boosting
therapy
PD.
Herein,
remarkable
promotion
biogenesis
and
improve
treatment
PD
by
using
mitochondria‐targeted
biomimetic
nanoparticles,
which
are
Cu
2‐
x
Se‐based
nanoparticles
functionalized
with
curcumin
wrapped
DSPE‐PEG
2000
‐TPP‐modified
macrophage
membrane
(denoted
as
CSCCT
NPs),
reported.
These
can
efficiently
target
mitochondria
damaged
in
an
inflammatory
environment,
mediate
signaling
pathway
NAD
+
/SIRT1/PGC‐1
α
/PPAR
γ
/NRF1/TFAM
alleviate
1‐methyl‐4‐phenylpyridinium
(MPP
)‐induced
neuronal
toxicity.
They
reduce
reactive
oxygen
species,
restore
potential
(MMP),
protect
integrity
respiratory
chain,
via
promoting
biogenesis,
synergistically
motor
disorders
anxiety
behavior
1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine
(MPTP)‐induced
mice.
This
study
demonstrates
that
targeting
has
a
great
mitochondria‐related
diseases.
Science Translational Medicine,
Год журнала:
2023,
Номер
15(711)
Опубликована: Авг. 30, 2023
Parkinson’s
disease
(PD)
is
the
most
common
neurodegenerative
movement
disorder,
and
neuroprotective
or
disease-modifying
interventions
remain
elusive.
High-throughput
markers
aimed
at
stratifying
patients
on
basis
of
shared
etiology
are
required
to
ensure
success
therapies
in
clinical
trials.
Mitochondrial
dysfunction
plays
a
prominent
role
pathogenesis
PD.
Previously,
we
found
brain
region–specific
accumulation
mitochondrial
DNA
(mtDNA)
damage
PD
neuronal
culture
animal
models,
as
well
human
postmortem
tissue.
To
investigate
mtDNA
potential
blood-based
marker
for
PD,
describe
herein
PCR-based
assay
(Mito
DX
)
that
allows
accurate
real-time
quantification
scalable
platform.
We
was
increased
peripheral
blood
mononuclear
cells
derived
from
with
idiopathic
those
harboring
PD-associated
leucine-rich
repeat
kinase
2
(
LRRK2
G2019S
mutation
comparison
age-matched
controls.
In
addition,
elevated
non–disease-manifesting
carriers,
demonstrating
can
occur
irrespective
diagnosis.
further
established
Lrrk2
knock-in
mice
displayed
damage,
whereas
knockout
showed
fewer
lesions
ventral
midbrain,
compared
wild-type
control
mice.
Furthermore,
small-molecule
inhibitor
mitigated
rotenone
rat
midbrain
neuron
model
patient–derived
lymphoblastoid
cell
lines.
Quantifying
using
Mito
may
have
utility
candidate
measuring
pharmacodynamic
response
inhibitors.
Archives of Toxicology,
Год журнала:
2024,
Номер
98(3), С. 579 - 615
Опубликована: Янв. 24, 2024
Abstract
This
article
provides
an
overview
of
the
background
knowledge
ferroptosis
in
nervous
system,
as
well
key
role
nuclear
factor
E2-related
2
(Nrf2)
regulating
ferroptosis.
The
takes
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Huntington's
(HD),
and
amyotrophic
lateral
sclerosis
(ALS)
starting
point
to
explore
close
association
between
Nrf2
ferroptosis,
which
is
clear
significant
importance
for
understanding
mechanism
neurodegenerative
diseases
(NDs)
based
on
oxidative
stress
(OS).
Accumulating
evidence
links
pathogenesis
NDs.
As
progresses,
damage
antioxidant
excessive
OS,
altered
expression
levels,
especially
inhibition
by
lipid
peroxidation
inhibitors
adaptive
enhancement
signaling,
demonstrate
potential
clinical
significance
detecting
identifying
targeted
therapy
neuronal
loss
mitochondrial
dysfunction.
These
findings
provide
new
insights
possibilities
treatment
prevention
