Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Фев. 19, 2024
Introduction
The
goal
of
this
study
is
to
explore
the
pharmacological
potential
amyloid-reducing
vasodilator
fasudil,
a
selective
Ras
homolog
(Rho)-associated
kinases
(ROCK)
inhibitor,
in
P301S
tau
transgenic
mouse
model
(Line
PS19)
neurodegenerative
tauopathy
and
Alzheimer's
disease
(AD).
Methods
We
used
LC-MS/MS,
ELISA
bioinformatic
approaches
investigate
effect
treatment
with
fasudil
on
brain
proteomic
profile
PS19
mice.
also
explored
efficacy
reducing
phosphorylation,
beneficial
and/or
toxic
effects
its
administration
Results
Proteomic
profiling
mice
brains
exposed
revealed
activation
mitochondrial
tricarboxylic
acid
(TCA)
cycle
blood-brain
barrier
(BBB)
gap
junction
metabolic
pathways.
observed
significant
negative
correlation
between
levels
phosphorylated
(pTau)
at
residue
396
both
metabolite
hydroxyfasudil.
Conclusions
Our
results
provide
evidence
proteins
pathways
related
mitochondria
BBB
functions
by
support
further
development
therapeutic
for
AD.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(23), С. 13144 - 13144
Опубликована: Дек. 6, 2024
The
efficacy
of
assisted
reproductive
technologies
(ARTs)
in
older
women
remains
constrained,
largely
due
to
an
incomplete
understanding
the
underlying
pathophysiology.
This
review
aims
consolidate
current
knowledge
on
age-associated
mitochondrial
alterations
and
their
implications
for
ovarian
aging,
with
emphasis
causes
DNA
(mtDNA)
mutations,
repair
mechanisms,
future
therapeutic
directions.
Relevant
articles
published
up
30
September
2024
were
identified
through
a
systematic
search
electronic
databases.
free
radical
theory
proposes
that
reactive
oxygen
species
(ROS)
inflict
damage
mtDNA
impair
function
essential
ATP
generation
oocytes.
Oocytes
face
prolonged
pressure
persisting
five
decades.
MtDNA
exhibits
limited
capacity
double-strand
break
repair,
heavily
depending
poly
ADP-ribose
polymerase
1
(PARP1)-mediated
single-strand
breaks.
process
depletes
nicotinamide
adenine
dinucleotide
(NAD⁺)
ATP,
creating
detrimental
cycle
where
continued
further
compromises
oocyte
functionality.
Interventions
interrupt
this
destructive
may
offer
preventive
benefits.
In
conclusion,
cumulative
burden
mutations
demands
can
lead
depletion
elevate
risk
aneuploidy,
ultimately
contributing
ART
failure
women.
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 14, 2025
Alzheimer’s
disease
(AD)
is
the
most
common
neurodegenerative
disorder,
accounting
for
approximately
70%
of
dementia
cases
worldwide.
Patients
gradually
exhibit
cognitive
decline,
such
as
memory
loss,
aphasia,
and
changes
in
personality
behavior.
Research
has
shown
that
mitochondrial
dysfunction
plays
a
critical
role
onset
progression
AD.
Mitochondrial
primarily
leads
to
increased
oxidative
stress,
imbalances
dynamics,
impaired
mitophagy,
genome
abnormalities.
These
abnormalities
are
closely
associated
with
amyloid-beta
tau
protein
pathology,
collectively
accelerating
process.
This
review
summarizes
mitochondria
development
AD,
latest
research
progress,
explores
potential
mitochondria-targeted
therapeutic
strategies
Targeting
mitochondria-related
pathways
may
significantly
improve
quality
life
AD
patients
future.
Antioxidants,
Год журнала:
2023,
Номер
12(4), С. 895 - 895
Опубликована: Апрель 6, 2023
Stroke
is
one
of
the
leading
causes
morbidity
and
mortality
worldwide.
A
main
cause
brain
damage
by
stroke
ischemia-reperfusion
(IR)
injury
due
to
increased
production
reactive
oxygen
species
(ROS)
energy
failure
caused
changes
in
mitochondrial
metabolism.
Ischemia
a
build-up
succinate
tissues
NADH:
ubiquinone
oxidoreductase
(complex
I)
activity
that
promote
reverse
electron
transfer
(RET),
which
portion
electrons
derived
from
are
redirected
ubiquinol
along
complex
I
reach
NADH
dehydrogenase
module
I,
where
matrix
NAD+
converted
excessive
ROS
produced.
RET
has
been
shown
play
role
macrophage
activation
response
bacterial
infection,
transport
chain
reorganization
supply,
carotid
body
adaptation
levels.
In
addition
stroke,
deregulated
RET-generated
(RET-ROS)
have
implicated
tissue
during
organ
transplantation,
whereas
an
RET-induced
NAD+/NADH
ratio
decrease
aging,
age-related
neurodegeneration,
cancer.
this
review,
we
provide
historical
account
roles
oxidative
pathogenesis
ischemic
summarize
latest
developments
our
understanding
biology
RET-associated
pathological
conditions,
discuss
new
ways
target
cancer,
neurodegenerative
diseases
modulating
RET.
Investigative Ophthalmology & Visual Science,
Год журнала:
2025,
Номер
66(1), С. 17 - 17
Опубликована: Янв. 8, 2025
Purpose:
Oxidative
phosphorylation
(OXPHOS)
is
an
aerobic
metabolic
mechanism,
and
its
dysfunction
plays
important
role
in
the
pathological
changes
of
ischemic
diseases.
However,
systematic
studies
on
occurrence
retinal
detachment
(RD)
are
lacking.
Methods:
Single-cell
RNA
sequencing
(scRNA-seq)
human
retina
was
performed
to
detect
various
cells
after
RD.
In
this
study,
animal
experiments
were
conducted
explore
OXPHOS
activity
addition,
idebenone,
a
coenzyme
Q10
(CoQ10)
analog
currently
used
treat
Leber
hereditary
optic
neuropathy
(LHON),
improve
disorder
experimental
RD
model.
Results:
ScRNA-seq
revealed
abnormal
energy
metabolism
pathways
Adenosine
triphosphate
(ATP)
reactive
oxygen
species
(ROS)
main
products
OXPHOS,
mouse
model
indicated
that
rise
ROS
levels
may
have
greater
impact
photoreceptors
early
stage,
whereas
decreased
ATP
synthesis
observed
later
stage;
these
threaten
function
morphology
retina.
Idebenone
administered
mice
intragastrically,
leading
reduced
stage
post-RD
improved
which
closely
related
maintenance
mitochondrial
morphology.
Conclusions:
leads
photoreceptor
degeneration
RD,
can
be
alleviated
by
improving
function.
