bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: June 7, 2023
In
this
paper
we
use
simulation
methods
to
study
a
hypothetical
uncoupling
agent
as
therapy
for
dementia.
We
simulate
the
proliferation
of
mitochondrial
deletion
mutants
amongst
population
wild-type
in
human
neurons.
Mitochondria
play
key
role
ATP
generation.
Clonal
expansion
can
lead
being
overwhelmed
by
deletions
such
that
diminished
no
longer
fulfill
cell's
energy
requirement,
eventually
leading
its
demise.
The
intention
is
reduce
formation
reducing
mutation
rate.
However,
consequence
production
efficacy
also
reduced
which
turn
increases
copy
number
order
compensate
deficit.
results
showed
severity
dementia,
however,
there
was
some
increase
cognitive
dysfunction
pre-onset
effectiveness
dependent
upon
timing
intervention
relative
onset
dementia
and
would
necessitate
predicting
many
years
advance.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 25, 2025
Spinal
cord
injury
is
characterized
by
high
incidence
and
disability,
the
specific
targets
drugs
have
not
yet
been
explored.
Lipid
droplet
a
type
of
organelles
that
regulates
lipid
metabolism
oxidative
stress.
And
regulatory
mechanisms
droplets
on
spinal
remain
unclear.
Herein,
it
found
GTPase
activation
Annexin
A7
(ANXA7)
promotes
up-regulation
genes
related
to
formation.
ANXA7
can
interact
with
peroxisome
proliferator-activated
receptor
gamma
(PPARγ)
enhance
stability
PPARγ,
promote
formation
interaction
mitochondria
through
promoting
Perilipin
5
expression.
Then,
stress
peroxidation
are
inhibited
due
promotion
nuclear
factor
erythroid
2-related
2
(NRF2)
translocation
expression
glutathione
peroxidase
4
(GPX4).
mitochondria-lipid
enhancing
which
contributes
inhibiting
neuron
damage.
Furthermore,
PPARγ
neural
function
recovery
repair
in
mice.
The
focus
this
study
investigate
effects
regulated
ANXA7/PPARγ,
providing
new
strategies
for
injury.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(20), P. 11315 - 11315
Published: Oct. 21, 2024
Compromised
mitochondrial
electron
transport
chain
(ETC)
activities
are
associated
with
depression
in
humans
and
rodents.
However,
the
effects
of
enhancement
ETC
on
remain
elusive.
We
recently
reported
that
an
extremely
low-frequency
electromagnetic
field
(ELF-EMF)
as
low
10
μT
induced
hormetic
activation
complexes
human/mouse
cultured
cells
mouse
livers.
Chronic
social
defeat
stress
(CSDS)
for
consecutive
days
caused
behavioral
defects
mimicking
mice,
using
ELF-EMF
two
to
six
weeks
ameliorated
them.
CSDS
variably
decreased
proteins
prefrontal
cortex
(PFC)
days,
which
were
increased
by
weeks.
had
no
effect
oxygen
consumption
rate
PFC
but
enhanced
it.
inactivated
SOD2
enhancing
its
acetylation
lipid
peroxidation
PFC.
In
contrast,
activated
Sirt3-FoxO3a-SOD2
pathway
suppressed
peroxidation.
Furthermore,
markers
mitophagy,
was
The
exerted
beneficial
energy
production,
antioxidation,
dynamics
a
model
depression.
envisage
is
promising
therapeutic
option
Journal of Mitochondria Plastids and Endosymbiosis,
Journal Year:
2024,
Volume and Issue:
2(1)
Published: Feb. 25, 2024
Oleoylethanolamide
(OEA)
is
an
endogenous
lipid
mediator
which
being
discussed
as
a
weight-loss
drug
for
obesity.
In
addition
to
its
homoeostatic
functions,
OEA
has
neuroprotective
and
anti-inflammatory
capabilities.
To
further
investigate
the
properties
of
against
neurodegenerative
diseases,
we
studied
influence
on
mitochondrial
function
with
focus
energy
metabolism
in
cellular
model
Alzheimer's
disease
(AD).
SH-SY5Y-APP695
cells
were
used
early
stage
AD.
Vector-transfected
SH-SY5Y-MOCK
served
controls.
Using
these
cells,
investigated
adenosine
triphosphate
(ATP)
production,
various
glucose-
fat-metabolising
genes
well
fatty
acid
oxidation
(FAO)
lactate/pyruvate
levels
treated
OEA.
Incubation
showed
significant
increase
ATP
both
cell
lines.
Pyruvate
dehydrogenase
1
gene
expression
was
significantly
decreased
whereas
FAO
ratio
increased
cells.
Based
concentration,
conclude
that
incubation
leads
disease-specific
higher
availability
this
seems
result
from
elevated
conversion
pyruvate
acetyl-CoA,
whilst
it
may
be
caused
by
lactate
level
more
FAO.
Frontiers in Neuroscience,
Journal Year:
2024,
Volume and Issue:
18
Published: Sept. 24, 2024
The
brain’s
high
demand
for
energy
necessitates
tightly
regulated
metabolic
pathways
to
sustain
physiological
activity.
Glucose,
the
primary
substrate,
undergoes
complex
transformations,
with
mitochondria
playing
a
central
role
in
ATP
production
via
oxidative
phosphorylation.
Dysregulation
of
this
interplay
is
implicated
Alzheimer’s
disease
(AD),
where
compromised
glucose
metabolism,
stress,
and
mitochondrial
dysfunction
contribute
progression.
This
review
explores
intricate
bioenergetic
crosstalk
between
astrocytes
neurons,
highlighting
function
uncoupling
proteins
(UCPs),
particularly
UCP4,
as
important
regulators
brain
metabolism
neuronal
function.
Predominantly
expressed
brain,
UCP4
reduces
membrane
potential
inner
membrane,
thereby
potentially
decreasing
generation
reactive
oxygen
species.
Furthermore,
mitigates
calcium
overload
sustains
cellular
levels
through
shift
from
respiration
glycolysis.
Interestingly,
UCPs,
UCP2,
4
5
are
significantly
reduced
AD
tissue
specific
variant
has
been
associated
an
increased
risk
developing
AD.
Few
studies
modulating
expression
or
neurons
have
highlighted
protective
effects
against
neurodegeneration
aging,
suggesting
that
pharmacological
strategies
aimed
at
activating
such
protonophoric
uncouplers,
hold
promise
therapeutic
interventions
other
neurodegenerative
diseases.
Despite
significant
advances,
our
understanding
UCPs
remains
its
early
stages,
emphasizing
need
further
research
unravel
their
biological
functions
potential.
Antioxidants,
Journal Year:
2024,
Volume and Issue:
13(11), P. 1343 - 1343
Published: Nov. 1, 2024
Alzheimer's
disease
(AD)
is
a
complex
neurodegenerative
disorder
that
classically
defined
by
the
extracellular
deposition
of
senile
plaques
rich
in
amyloid-beta
(Aβ)
protein
and
intracellular
accumulation
neurofibrillary
tangles
(NFTs)
are
aberrantly
modified
tau
protein.
In
addition
to
aggregative
proteostatic
abnormalities,
neurons
affected
AD
also
frequently
possess
dysfunctional
mitochondria
disrupted
mitochondrial
maintenance,
such
as
inability
eliminate
damaged
via
mitophagy.
Decades
have
been
spent
interrogating
etiopathogenesis
AD,
contributions
from
model
organism
research
aided
developing
more
fundamental
understanding
molecular
dysfunction
caused
Aβ
toxic
aggregates.
The
soil
nematode
