Zooming in on brain inflammation in Alzheimer’s disease
Brain,
Год журнала:
2025,
Номер
148(1), С. 1 - 2
Опубликована: Янв. 1, 2025
Язык: Английский
Network Diffusion-Constrained Variational Generative Models for Investigating the Molecular Dynamics of Brain Connectomes Under Neurodegeneration
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1062 - 1062
Опубликована: Янв. 26, 2025
Alzheimer’s
disease
(AD)
is
a
complex
and
progressive
neurodegenerative
condition
with
significant
societal
impact.
Understanding
the
temporal
dynamics
of
its
pathology
essential
for
advancing
therapeutic
interventions.
Empirical
anatomical
evidence
indicates
that
network
decoupling
occurs
as
result
gray
matter
atrophy.
However,
scarcity
longitudinal
clinical
data
presents
challenges
computer-based
simulations.
To
address
this,
first-principles-based,
physics-constrained
Bayesian
framework
proposed
to
model
time-dependent
connectome
during
neurodegeneration.
This
diffusion
segments
pathological
progression
into
discrete
time
windows
optimizes
distributions
biomarker
regression,
conceptualized
learning
problem.
The
employs
variational
autoencoder-like
architecture
computational
enhancements
stabilize
improve
training
efficiency.
Experimental
evaluations
demonstrate
meta-models
outperform
traditional
static
models.
models
were
evaluated
using
both
synthetic
real-world
MRI
PET
datasets
measure
amyloid
beta,
tau,
glucose
metabolism.
successfully
distinguishes
normative
aging
from
AD
pathology.
Findings
provide
novel
support
“decoupling”
hypothesis
reveal
eigenvalue-based
destabilization
in
AD.
Future
optimization
model,
integrated
data,
expected
applications
personalized
medicine
other
diseases.
Язык: Английский
Anti-Neuroinflammatory Eremophilane Sesquiterpenoids from Marine-Derived Fungus Phoma sp. DXH009
Marine Drugs,
Год журнала:
2025,
Номер
23(3), С. 94 - 94
Опубликована: Фев. 20, 2025
Three
new
eremophilane
sesquiterpenoids
(1–3),
together
with
six
known
analogues,
were
isolated
from
the
marine-derived
fungus
Phoma
sp.
DXH009.
Their
structures
elucidated
through
detailed
NMR
and
MS
spectroscopic
analysis,
absolute
configurations
of
1–4
determined
by
conformational
analysis
quantum
chemical
TDDFT-ECD
calculation.
anti-neuroinflammatory
activities
evaluated
using
lipopolysaccharide
(LPS)-induced
BV2
microglial
cells.
The
results
indicated
that
compound
5
(dihydrosporogen
AO-1)
exhibited
significant
inhibitory
effects
on
production
nitric
oxide
(NO)
levels
(EC50
=
3.11
μM)
less
cytotoxicity,
leading
to
a
reversal
effect
in
inducing
microphage
polarization
LPS-treated
These
correlated
suppressions
canonical
NF-κB
pathway
as
well
expression
key
neuroinflammatory
markers,
including
COX2,
TNF-α,
IL-6,
IL-1β.
Correspondingly,
treating
LPS-induced
mice
efficiently
ameliorated
neuroinflammation
tissues
cortex
hippocampus.
findings
suggest
sesquiterpenoid
could
be
potential
candidate
for
development
drugs.
Язык: Английский
NLRP3 inflammasome in neuroinflammation and central nervous system diseases
Cellular and Molecular Immunology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Abstract
Neuroinflammation
plays
an
important
role
in
the
pathogenesis
of
various
central
nervous
system
(CNS)
diseases.
The
NLRP3
inflammasome
is
intracellular
multiprotein
complex
composed
innate
immune
receptor
NLRP3,
adaptor
protein
ASC,
and
protease
caspase-1.
activation
can
induce
pyroptosis
release
proinflammatory
cytokines
IL-1β
IL-18,
thus
playing
a
inflammatory
responses.
Recent
studies
have
revealed
that
activated
brain
to
neuroinflammation,
leading
further
neuronal
damage
functional
impairment,
contributes
pathological
process
neurological
diseases,
such
as
multiple
sclerosis,
Parkinson’s
disease,
Alzheimer’s
stroke.
In
this
review,
we
summarize
neuroinflammation
course
CNS
diseases
discuss
potential
approaches
target
for
treatment
Язык: Английский
Mechanisms and Emerging Regulators of Neuroinflammation: Exploring New Therapeutic Strategies for Neurological Disorders
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
47(1), С. 8 - 8
Опубликована: Дек. 26, 2024
Neuroinflammation
is
a
complex
and
dynamic
response
of
the
central
nervous
system
(CNS)
to
injury,
infection,
disease.
While
acute
neuroinflammation
plays
protective
role
by
facilitating
pathogen
clearance
tissue
repair,
chronic
dysregulated
inflammation
contributes
significantly
progression
neurodegenerative
disorders
such
as
Alzheimer's
disease,
Parkinson's
Multiple
Sclerosis.
This
review
explores
cellular
molecular
mechanisms
underlying
neuroinflammation,
focusing
on
roles
microglia,
astrocytes,
peripheral
immune
cells.
Key
signaling
pathways,
including
NF-κB,
JAK-STAT,
NLRP3
inflammasome,
are
discussed
alongside
emerging
regulators
non-coding
RNAs,
epigenetic
modifications,
gut-brain
axis.
The
therapeutic
landscape
evolving,
with
traditional
anti-inflammatory
drugs
like
NSAIDs
corticosteroids
offering
limited
efficacy
in
conditions.
Immunomodulators,
gene
RNA-based
therapeutics,
stem
cell
methods
have
all
shown
promise
for
more
specific
effective
interventions.
Additionally,
modulation
metabolic
states
gut
microbiota
has
emerged
novel
strategy
regulate
neuroinflammation.
Despite
significant
progress,
challenges
remain
translating
these
findings
into
clinically
viable
therapies.
Future
studies
should
concentrate
integrated,
interdisciplinary
reduce
slowing
disorders,
providing
opportunities
revolutionary
advances
CNS
Язык: Английский