Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer's disease through modulation of Dgat2
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 19, 2025
Abstract
Alzheimer’s
disease
(AD)
is
a
progressive
neurodegenerative
disorder
characterized
by
amyloid-β
(Aβ)
plaque
accumulation,
cognitive
decline,
lipid
dysregulation,
and
neuroinflammation.
Mutations
in
the
Amyloid
Precursor
Protein
(APP),
accumulation
of
A
β42
contribute
to
AD,
however,
underlying
mechanisms
linking
beta
amyloid
metabolism
neuroinflammation
remain
unclear.
Using
Drosophila
models,
we
demonstrate
that
App
NLG
Aβ42
lead
locomotor
impairments,
disrupted
sleep
activity,
memory
deficits,
loss
synaptic
integrity,
Lipid
have
also
been
observed
NLG-F
knockin
mouse
model,
supporting
their
involvement
AD
pathogenesis.
Furthermore,
role
Diacylglycerol
O-acyltransferase
2
(Dgat2),
key
enzyme
regulation,
modulating
phenotypes,
as
Dgat2
levels
its
potential
transcription
factors
were
altered
models.
In
knockdown
reduced
restored
improved
function,
attenuated
Additionally,
modulation
quality
circadian
rhythms,
further
implicating
progression.
mice,
inhibition
mitigated
dysmetabolism
decreased
neuroinflammatory
responses,
expression
risk
genes.
These
findings
underscore
intricate
interplay
between
pathology,
neuroinflammation,
suggest
targeting
may
provide
novel
therapeutic
strategy
for
mitigating
AD-associated
dysfunction.
Understanding
conserved
impact
homeostasis
across
species
offers
valuable
insights
into
translational
interventions
AD.
Язык: Английский
Unraveling the Pathogenesis of Post‐Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK‐STAT Signaling
Advanced Science,
Год журнала:
2024,
Номер
11(33)
Опубликована: Июль 1, 2024
Post-stroke
depression
is
a
common
complication
that
imposes
significant
burdens
and
challenges
on
patients.
The
occurrence
of
often
associated
with
frontal
lobe
hemorrhage,
however,
current
understanding
the
underlying
mechanisms
remains
limited.
Here,
pathogenic
circuitry
connectivity,
electrophysiological
alterations,
molecular
characteristics
are
investigated
related
to
in
adult
male
mice
following
unilateral
injection
blood
medial
prefrontal
cortex
(mPFC).
It
demonstrated
specific
neurological
hematoma
model
mPFC,
ventral
tegmental
area
(VTA)
shows
higher
percentage
connectivity
disruption
compared
lateral
habenula
(LHb)
striatum
(STR).
Additionally,
long-range
projections
originating
from
demonstrate
damage
percentages
within
connections
between
each
region
mPFC.
mPFC
neurons
reveal
reduced
neuronal
excitability
altered
synaptic
communication.
Furthermore,
transcriptomic
analysis
identifies
involvement
Janus
Kinase-Signal
Transducer
Activator
Transcription
(JAK-STAT)
signaling
pathway,
targeting
JAK-STAT
pathway
significantly
alleviates
severity
depressive
symptoms.
These
findings
improve
post-hemorrhagic
may
guide
development
efficient
treatments.
Язык: Английский