Frontiers in Molecular Neuroscience,
Год журнала:
2025,
Номер
17
Опубликована: Янв. 22, 2025
Parkinson’s
disease
(PD)
involves
the
disruption
of
brain
energy
homeostasis.
This
encompasses
broad-impact
factors
such
as
mitochondrial
dysfunction,
impaired
glycolysis,
and
other
metabolic
disturbances,
like
disruptions
in
pentose
phosphate
pathway
purine
metabolism.
Cortical
hubs,
which
are
highly
connected
regions
essential
for
coordinating
multiple
functions,
require
significant
due
to
their
dense
synaptic
activity
long-range
connections.
Deficits
ATP
production
PD
can
severely
impair
these
hubs.
The
imbalance
also
affects
subcortical
regions,
including
massive
axonal
arbors
striatum
substantia
nigra
pars
compacta
neurons,
high
demand.
decline
may
result
α
-synuclein
accumulation,
autophagy-lysosomal
system
impairment,
neuronal
network
breakdown
accelerated
neurodegeneration.
We
propose
an
“ATP
Supply–Demand
Mismatch
Model”
help
explain
pathogenesis
PD.
model
emphasizes
how
deficits
drive
pathological
protein
aggregation,
autophagy,
degeneration
key
networks,
contributing
both
motor
non-motor
symptoms.
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Апрель 3, 2023
Repetitive
physical
insults
to
the
head,
including
those
that
elicit
mild
traumatic
brain
injury
(mTBI),
are
a
known
risk
factor
for
variety
of
neurodegenerative
conditions
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
and
chronic
encephalopathy
(CTE).
Although
most
individuals
who
sustain
mTBI
typically
achieve
seemingly
full
recovery
within
few
weeks,
subset
experience
delayed-onset
symptoms
later
in
life.
As
research
has
focused
on
acute
phase
injury,
there
is
an
incomplete
understanding
mechanisms
related
late-life
emergence
neurodegeneration
after
early
exposure
head
trauma.
The
recent
adoption
Drosophila
-based
models
provides
several
unique
advantages
over
existing
preclinical
animal
models,
tractable
framework
amenable
high-throughput
assays
short
relative
lifespan
conducive
lifelong
mechanistic
investigation.
use
flies
also
opportunity
investigate
important
factors
associated
with
conditions,
specifically
age
sex.
In
this
review,
we
survey
current
literature
examines
sex
as
contributing
trauma-mediated
humans
mammalian
models.
We
discuss
similarities
disparities
between
human
fly
aging,
differences,
pathophysiology.
Finally,
highlight
effective
tool
investigating
underlying
trauma-induced
identifying
therapeutic
targets
treatment
recovery.
Drug Development Research,
Год журнала:
2023,
Номер
84(6), С. 1159 - 1174
Опубликована: Май 12, 2023
Growing
evidence
points
to
impaired
autophagy
as
one
of
the
major
factors
implicated
in
pathophysiology
Parkinson's
disease
(PD).
Autophagy
is
a
downstream
target
adenosine
monophosphate-activated
protein
kinase
(AMPK).
Inosine
has
already
demonstrated
neuroprotective
effect
against
neuronal
loss
neurodegenerative
diseases,
mainly
due
its
anti-inflammatory
and
antioxidant
properties.
We,
herein,
aimed
at
investigating
effects
inosine
rotenone-induced
PD
rats
focus
on
activation
AMPK-mediated
autophagy.
successfully
increased
p-AMPK/AMPK
ratio
improved
their
motor
performance
muscular
co-ordination
(assessed
by
rotarod,
open
field,
grip
strength
tests,
well
manual
gait
analysis).
Furthermore,
was
able
mitigate
histopathological
alterations
restore
tyrosine
hydroxylase
immunoreactivity
rats'
substantia
nigra.
Inosine-induced
AMPK
resulted
an
enhancement,
striatal
Unc-S1-like
kinase1
beclin-1
expression,
also
increment
light
chain
3II
3I
ratio,
along
with
decline
mammalian
rapamycin
p62
expressions.
The
inosine-induced
stimulation
attenuated
apoptosis
promoted
activity.
Unsurprisingly,
these
were
antagonized
preadministration
dorsomorphin
(an
inhibitor).
In
conclusion,
exerted
via
through
restoration
imbalance
between
apoptosis.
These
findings
support
potential
application
treatment.
Frontiers in Molecular Neuroscience,
Год журнала:
2025,
Номер
17
Опубликована: Янв. 22, 2025
Parkinson’s
disease
(PD)
involves
the
disruption
of
brain
energy
homeostasis.
This
encompasses
broad-impact
factors
such
as
mitochondrial
dysfunction,
impaired
glycolysis,
and
other
metabolic
disturbances,
like
disruptions
in
pentose
phosphate
pathway
purine
metabolism.
Cortical
hubs,
which
are
highly
connected
regions
essential
for
coordinating
multiple
functions,
require
significant
due
to
their
dense
synaptic
activity
long-range
connections.
Deficits
ATP
production
PD
can
severely
impair
these
hubs.
The
imbalance
also
affects
subcortical
regions,
including
massive
axonal
arbors
striatum
substantia
nigra
pars
compacta
neurons,
high
demand.
decline
may
result
α
-synuclein
accumulation,
autophagy-lysosomal
system
impairment,
neuronal
network
breakdown
accelerated
neurodegeneration.
We
propose
an
“ATP
Supply–Demand
Mismatch
Model”
help
explain
pathogenesis
PD.
model
emphasizes
how
deficits
drive
pathological
protein
aggregation,
autophagy,
degeneration
key
networks,
contributing
both
motor
non-motor
symptoms.
