Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(14)
Опубликована: Июнь 6, 2023
Alzheimer's
disease
(AD)
is
the
most
common
cause
of
dementia.
The
APOE-ε4
allele
apolipoprotein
E
(APOE)
gene
strongest
genetic
risk
factor
for
late-onset
AD.
APOE
genotype
modulates
effect
sleep
disruption
on
AD
risk,
suggesting
a
possible
link
between
apoE
and
in
pathogenesis,
which
relatively
unexplored.
We
hypothesized
that
modifies
Aβ
deposition
plaque-associated
tau
seeding
spreading
form
neuritic
plaque-tau
(NP-tau)
pathology
response
to
chronic
deprivation
(SD)
an
isoform-dependent
fashion.
To
test
this
hypothesis,
we
used
APPPS1
mice
expressing
human
APOE-ε3
or
-ε4
with
without
AD-tau
injection.
found
SD
significantly
increased
peri-plaque
NP-tau
presence
APOE4
but
not
APOE3.
decreased
microglial
clustering
around
plaques
aquaporin-4
(AQP4)
polarization
blood
vessels
also
sleep-deprived
APPPS1:E4
injected
had
altered
behaviors
compared
APPPS1:E3
mice.
These
findings
suggest
critical
modifier
development
SD.
Nature Neuroscience,
Год журнала:
2024,
Номер
27(4), С. 666 - 678
Опубликована: Фев. 15, 2024
Abstract
Sleep
is
thought
to
be
restorative
brain
energy
homeostasis,
but
it
not
clear
how
this
achieved.
We
show
here
that
Drosophila
glia
exhibit
a
daily
cycle
of
glial
mitochondrial
oxidation
and
lipid
accumulation
dependent
on
prior
wake
requires
the
APOE
orthologs
NLaz
GLaz,
which
mediate
neuron–glia
transfer.
In
turn,
full
night
sleep
required
for
clearance,
oxidative
recovery
maximal
neuronal
mitophagy.
Knockdown
causes
stress
accumulate
in
neurons,
integrity
protein,
Drp1,
accumulation.
These
data
suggest
neurons
avoid
damage
during
by
using
mitophagy
passing
form
lipids.
propose
metabolic
between
reflects
fundamental
function
relevant
homeostasis.
Annals of Neurology,
Год журнала:
2024,
Номер
95(4), С. 625 - 634
Опубликована: Янв. 5, 2024
Alzheimer's
disease
(AD)
is
the
most
common
neurodegenerative
disorder
and
one
of
leading
causes
disability
worldwide.
The
apolipoprotein
E4
gene
(APOE4)
strongest
genetic
risk
factor
for
AD.
In
2023,
APOE4
National
Institute
on
Aging/Alzheimer's
Disease
Sequencing
Project
working
group
came
together
to
gather
data
discuss
question
whether
reduce
or
increase
as
a
therapeutic
intervention
It
was
unanimous
consensus
that
cumulative
from
multiple
studies
in
humans
animal
models
support
lowering
should
be
target
approaches
carriers.
ANN
NEUROL
2024;95:625-634.
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Янв. 13, 2025
Lipid
droplets
(LDs),
serving
as
the
convergence
point
of
energy
metabolism
and
multiple
signaling
pathways,
have
garnered
increasing
attention
in
recent
years.
Different
cell
types
within
central
nervous
system
(CNS)
can
regulate
to
generate
or
degrade
LDs
response
diverse
pathological
stimuli.
This
article
provides
a
comprehensive
review
on
composition
CNS,
their
generation
degradation
processes,
interaction
mechanisms
with
mitochondria,
distribution
among
different
types,
roles
played
by
these
cells-particularly
microglia
astrocytes-in
various
prevalent
neurological
disorders.
Additionally,
we
also
emphasize
paradoxical
role
post-cerebral
ischemia
inflammation
explore
potential
underlying
mechanisms,
aiming
identify
novel
therapeutic
targets
for
this
disease.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Авг. 25, 2023
Alzheimer's
disease,
the
most
common
age-related
neurodegenerative
is
characterized
by
tau
aggregation
and
associated
with
disrupted
circadian
rhythms
dampened
clock
gene
expression.
REV-ERBα
a
core
protein
which
also
serves
as
nuclear
receptor
transcriptional
repressor
involved
in
lipid
metabolism
macrophage
function.
Global
deletion
has
been
shown
to
promote
microglial
activation
mitigate
amyloid
plaque
formation.
However,
cell-autonomous
effects
of
healthy
brain
tauopathy
are
unexplored.
Here,
we
show
that
enhances
inflammatory
signaling,
disrupts
metabolism,
causes
droplet
(LD)
accumulation
specifically
male
microglia.
These
events
impair
phagocytosis,
can
be
partially
rescued
blockage
LD
In
vivo,
exacerbates
neuroinflammation
two
mouse
models,
mice.
data
demonstrate
importance
droplets
reveal
therapeutically
accessible,
sex-dependent
regulator
tauopathy.
Biomolecules,
Год журнала:
2023,
Номер
13(2), С. 313 - 313
Опубликована: Фев. 7, 2023
The
deposition
of
amyloid-beta
(Aβ)
plaques
in
the
brain
is
one
primary
pathological
characteristics
Alzheimer’s
disease
(AD).
It
can
take
place
20–30
years
before
onset
clinical
symptoms.
imbalance
between
production
and
clearance
Aβ
major
causes
AD.
Enhancing
at
an
early
stage
attractive
preventive
therapeutic
strategy
Direct
inhibition
aggregation
using
small
molecules,
peptides,
monoclonal
antibody
drugs
has
not
yielded
satisfactory
efficacy
trials
for
decades.
Novel
approaches
are
required
to
understand
combat
deposition.
Neurological
dysfunction
a
complex
process
that
integrates
functions
different
types
cells
brain.
role
non-neurons
AD
been
fully
elucidated.
An
in-depth
understanding
interactions
neurons
contribute
elucidation
formation
identification
effective
drug
targets.
patient-derived
pluripotent
stem
(PSCs)
contain
complete
background
information
have
potential
differentiate
into
various
vitro,
which
may
bring
new
insight
treatment
Here,
we
systematically
review
latest
studies
on
clarify
roles
cell
among
microglia,
astroglia
response
plaques,
will
be
beneficial
explore
methods
reconstructing
models
inducible
PSCs
(iPSCs)
through
differentiation
techniques
validating
applications
plaques.
This
provide
most
promising
directions
finding
clues
preventing
delaying
development
