Recent Insights on the Role of Nuclear Receptors in Alzheimer’s Disease: Mechanisms and Therapeutic Application
Xiaoxiao Shan,
Dawei Li,
Huihui Yin
и другие.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1207 - 1207
Опубликована: Янв. 30, 2025
Nuclear
receptors
(NRs)
are
ligand-activated
transcription
factors
that
regulate
a
broad
array
of
biological
processes,
including
inflammation,
lipid
metabolism,
cell
proliferation,
and
apoptosis.
Among
the
diverse
family
NRs,
peroxisome
proliferator-activated
(PPARs),
estrogen
receptor
(ER),
liver
X
(LXR),
farnesoid
(FXR),
retinoid
(RXR),
aryl
hydrocarbon
(AhR)
have
garnered
significant
attention
for
their
roles
in
neurodegenerative
diseases,
particularly
Alzheimer’s
disease
(AD).
NRs
influence
pathophysiology
AD
through
mechanisms
such
as
modulation
amyloid-beta
(Aβ)
deposition,
regulation
inflammatory
pathways,
improvement
neuronal
function.
However,
dual
role
progression,
where
some
may
exacerbate
while
others
offer
therapeutic
potential,
presents
critical
challenge
application
treatment.
This
review
explores
functional
diversity
highlighting
involvement
AD-related
processes
discussing
prospects
NR-targeting
strategies.
Furthermore,
key
challenges,
necessity
precise
identification
beneficial
detailed
structural
analysis
molecular
dynamics
simulations,
further
investigation
NR
AD,
tau
pathology
autophagy,
also
discussed.
Collectively,
continued
research
is
essential
to
clarify
ultimately
facilitating
potential
use
diagnosis,
prevention,
treatment
AD.
Язык: Английский
Hyperintensity of the left piriform cortex and amygdala on T2-weighted FLAIR images in patients with probable Alzheimer’s disease correlates with cerebral cortical atrophy
Acta Radiologica Open,
Год журнала:
2025,
Номер
14(2)
Опубликована: Фев. 1, 2025
Background
The
left
piriform
cortex
and
amygdala
(PC&A)
tend
to
be
slightly
hyperintense
relative
the
right
PC&A
on
T2-weighted
fluid-attenuated
inversion
recovery
(T2W-FLAIR)
images
in
patients
with
probable
Alzheimer’s
disease
(pAD).
This
likely
represents
antecedent
thus
advanced
degeneration
of
PC&A.
Purpose
To
investigate
relationship
between
hyperintensities
cerebral
cortical
atrophy
magnetic
resonance
(MR)
voxel-based
morphometry
pAD
discuss
how
this
finding
could
relate
AD
progression.
Material
Methods
Patients
(
n
=
47;
age
range
68–93
years,
mean
80.8
±
6.7
years;
14
men
33
women)
who
underwent
T2W-FLAIR
imaging
MR
morphometric
study
using
a
specific
regional
analysis
system
for
(VSRAD)
were
retrospectively
examined.
measure
signal
intensity
ratios
(L-PC&A/R-PC&A),
regions
interest
(ROIs)
set
transaxial
which
both
PC&As
most
broadly
depicted;
ROIs
defined
as
large
possible.
Correlations
L-PC&A/R-PC&A
medial
temporal
lobe
(MTLCA)
well
whole
(WCCA)
VSRAD
determined.
Correlation
was
also
Results
correlated
MTLCA
(r
0.375,
p
.010,
95%
confidence
interval
[CI]
0.095–0.600)
WCCA
0.576,
<
.001,
CI
0.343–0.742).
did
not
correlate
0.013,
.932,
−0.282–0.305).
Conclusion
Left-sided
dominance
appeared
accelerate
progression
stages.
Язык: Английский
The dual role of microglia in Alzheimer’s disease: from immune regulation to pathological progression
Frontiers in Aging Neuroscience,
Год журнала:
2025,
Номер
17
Опубликована: Март 27, 2025
Alzheimer’s
disease
(AD)
is
a
widespread
neurodegenerative
disorder
and
one
of
the
major
challenges
for
public
health.
Despite
extensive
research,
role
microglia
in
AD
remains
complex
dual.
The
aim
this
review
to
summarize
most
recent
advances
research
regarding
dual
concerning
both
immunomodulation
pathological
progression
by
considering
mechanisms
activation
microglia,
effects
on
Aβ
clearance,
tau
pathology,
impacts
due
genetic
variations
microglial
functions.
Among
these
findings
are
status
M1
M2
phenotypes,
crucial
that
variants
like
TREM2
have
modulating
response
microglia.
This
describes
how
modulation
signaling
pathway
might
be
exploited
therapeutically
treatment
underlines
relevance
personalized
medicine
approach.
Язык: Английский
Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway
Molecules,
Год журнала:
2025,
Номер
30(7), С. 1555 - 1555
Опубликована: Март 31, 2025
Inflammation
contributes
to
the
onset
and
development
of
many
diseases,
including
neurodegenerative
caused
by
activation
microglia,
leading
neurological
deterioration.
Nuclear
factor-κB
(NF-κB)
is
one
most
relevant
pathways
for
identifying
anti-inflammatory
molecules.
In
this
study,
polygodial
isotadeonal,
two
drimane
sesquiterpene
dialdehydes,
were
isolated
from
Drimys
winteri,
a
medicinal
tree
Mapuche
people
in
Chile.
Isotadeonal,
or
epi-polygodial,
was
obtained
epimerization
basic
media
(60%
yield,
Na2CO3,
r/t,
24
h).
Both
sesquiterpenoids
evaluated
on
NF-κB
pathway,
with
result
that
isotadeonal
inhibited
phosphorylation
IκB-α
at
10
μM
higher
potency
Western
blotting.
The
final
inhibition
pathway
using
SEAP
reporter
(secreted
alkaline
phosphatase)
THP-1
cells.
Isotadeonal
than
polygodial,
quercetin,
CAPE
(phenethyl
ester
caffeic
acid).
silico
analysis
suggests
α-aldehyde
adopts
more
stable
conformation
active
pocket
polygodial.
Язык: Английский
Carvacrol/thymol derivatives as highly selective BuChE inhibitors with anti-inflammatory activities: Discovery and bio-evaluation
Bioorganic Chemistry,
Год журнала:
2025,
Номер
unknown, С. 108430 - 108430
Опубликована: Апрель 1, 2025
Язык: Английский
Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 11272 - 11272
Опубликована: Окт. 19, 2024
Recent
studies
underscore
the
role
of
gut
and
oral
microbiota
in
influencing
neuroinflammation
through
microbiota–gut–brain
axis,
including
Alzheimer’s
disease
(AD).
This
review
aims
to
provide
a
comprehensive
synthesis
recent
findings
on
involvement
neuroinflammatory
processes
associated
with
AD,
emphasizing
novel
insights
therapeutic
implications.
reveals
that
dysbiosis
AD
patients’
is
linked
heightened
peripheral
central
inflammatory
responses.
Specific
bacterial
taxa,
such
as
Bacteroides
Firmicutes
gut,
well
Porphyromonas
gingivalis
cavity,
are
notably
altered
leading
significant
changes
microglial
activation
cytokine
production.
Gut
alterations
increased
intestinal
permeability,
facilitating
translocation
endotoxins
like
lipopolysaccharides
(LPS)
into
bloodstream
exacerbating
by
activating
brain’s
toll-like
receptor
4
(TLR4)
pathways.
Furthermore,
microbiota-derived
metabolites,
short-chain
fatty
acids
(SCFAs)
amyloid
peptides,
can
cross
blood-brain
barrier
modulate
While
microbial
amyloids
may
contribute
amyloid-beta
aggregation
brain,
certain
SCFAs
butyrate
exhibit
anti-inflammatory
properties,
suggesting
potential
avenue
mitigate
neuroinflammation.
not
only
highlights
critical
pathology
but
also
offers
ray
hope
modulating
could
represent
strategy
for
reducing
slowing
progression.
Язык: Английский
Photobiomodulation regulates astrocyte activity and ameliorates scopolamine-induced cognitive behavioral decline
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Сен. 20, 2024
Introduction
The
pathophysiological
mechanism
of
Alzheimer’s
disease
(AD)
has
not
been
clearly
identified,
and
effective
treatment
methods
have
yet
established.
Scopolamine
causes
cholinergic
dysfunction
in
the
brain,
including
accumulation
amyloid-beta
plaques,
thereby
increasing
oxidative
stress
neuroinflammation,
mimicking
AD.
Glial
cells
such
as
astrocytes
recently
identified
possible
biomarkers
for
Photobiomodulation
(PBM)
elicits
a
beneficial
biological
response
tissues.
PBM
effects
on
central
nervous
system
(CNS)
widely
researched,
astrocyte
activity.
Methods
In
present
study,
was
performed
using
light
at
near-infrared
wavelength
825
nm.
Morris
water
maze
Y-maze
tests
were
employed
to
evaluate
cognitive
function
decline
scopolamine-induced
memory
model
its
improvement
with
PBM.
addition,
alteration
mitogen-activated
protein
kinase
(MAPK)
pathway
immunofluorescence
expression
levels
active
observed
hippocampus,
which
is
one
areas
affected
by
AD,
action
Results
A
reduction
neuronal
cell
death
hippocampus
caused
scopolamine
Moreover,
MAPK
pathway-related
marker
changes
glial
fibrillary
acidic
(an
marker)
PBM-treated
group.
Finally,
significant
correlations
between
functional
histological
results
found,
validating
results.
Discussion
These
findings
indicate
possibility
behavioral
due
CNS
alteration,
mimics
This
could
be
related
neuroinflammatory
modulation
altered
Язык: Английский
Optimization of microRNA Target Sequence Arrangement in AAV Vectors Dramatically Enhances Specificity and Efficiency of Transgene Expression in Cortical Microglia
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
Abstract
Microglia
play
a
critical
role
in
diseases
such
as
Alzheimer’s
and
stroke,
making
them
significant
target
for
therapeutic
intervention.
However,
due
to
their
immune
functions
detecting
combating
viral
invasion,
efficient
gene
delivery
microglia
remains
challenging.
We
achieved
specific
using
an
adeno-
associated
virus
(AAV)
vector
designed
this
purpose.
This
microglia-targeting
AAV
includes
the
mouse
microglia/macrophage-specific
ionized
calcium-binding
adaptor
molecule
1
(mIba1)
promoter,
green
fluorescent
protein
(GFP),
microRNA
sequences
(miR.Ts),
woodchuck
hepatitis
posttranscriptional
regulatory
element
(WPRE),
polyadenylation
(polyA)
signal,
positioned
between
inverted
terminal
repeats.
When
miR.Ts
were
placed
downstream
of
WPRE
(between
polyA),
expression
occurred
not
only
but
also
substantial
number
neurons.
when
upstream
GFP
WPRE)
or
on
both
sides
WPRE,
neuronal
was
significantly
suppressed,
resulting
selective
microglia.
Notably,
positioning
over
90%
specificity
more
than
60%
efficiency
transgene
three
weeks
after
administration.
enabled
GCaMP
microglia,
facilitating
real-time
monitoring
calcium
dynamics
microglial
process
activity
cortex.
Additionally,
intravenous
administration
with
blood-brain
barrier-penetrant
AAV-9P31
capsid
variant
resulted
extensive
selectively
throughout
brain.
These
findings
establish
system
robust
tool
long-term,
specific,
Язык: Английский