Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics
Biomedicines,
Год журнала:
2025,
Номер
13(2), С. 279 - 279
Опубликована: Янв. 23, 2025
Alzheimer’s
disease
(AD)
is
traditionally
viewed
through
the
lens
of
amyloid
cascade
hypothesis,
implicating
amyloid-beta
and
tau
protein
aggregates
as
main
pathological
culprits.
However,
burgeoning
research
points
to
brain’s
resident
immune
cells,
microglia,
critical
players
in
AD
pathogenesis,
progression,
potential
therapeutic
interventions.
This
review
examines
dynamic
roles
microglia
within
intricate
framework
AD.
We
detail
involvement
these
cells
neuroinflammation,
explaining
how
their
activation
response
fluctuations
may
influence
trajectory.
further
elucidate
complex
relationship
between
pathology.
study
highlights
dual
nature
which
contribute
both
aggregation
clearance
protein.
Moreover,
an
in-depth
analysis
interplay
unveils
significant,
yet
often
overlooked,
impact
this
interaction
on
neurodegeneration
Shifting
from
conventional
approaches,
we
assess
current
treatments
primarily
targeting
introduce
novel
strategies
that
involve
manipulating
microglial
functions.
These
innovative
methods
herald
a
paradigm
shift
management
Finally,
explore
field
precision
diagnosis
pursuit
robust
biomarkers.
underline
more
profound
comprehension
biology
could
enrich
essential
areas,
potentially
paving
way
for
accurate
diagnostic
tools
tailored
treatment
strategies.
In
conclusion,
expands
perspective
pathology
treatment,
drawing
attention
multifaceted
microglia.
As
continue
enhance
our
understanding
microglial-focused
interventions
emerge
promising
frontier
bolster
arsenal
fight
against
Язык: Английский
Blood-based biomarkers in mild behavioral impairment: an updated overview
Frontiers in Neurology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 6, 2025
Identifying
individuals
at-risk
for
dementia
is
one
of
the
critical
objectives
current
research
efforts,
highlighting
need
simple,
cost-effective,
and
minimally
invasive
biomarkers.
Mild
behavioral
impairment
(MBI),
characterized
by
emergence
persistent
neuropsychiatric
manifestations
in
older
adults,
has
attracted
increasing
attention
as
a
potential
early
indicator
cognitive
decline
dementia.
A
growing
number
studies
have
recently
begun
to
explore
relationship
between
MBI
several
blood-based
biomarkers
associated
with
Alzheimer's
disease
(AD)
pathology,
neurodegeneration,
well
systemic
metabolic
inflammatory
dysregulation.
In
this
context,
been
lower
plasma
Aβ42/Αβ40
ratio,
higher
phosphorylated
tau
at
threonine
181
(p-tau181),
increased
neurofilament
light
chain
(NfL)
levels,
disturbances
markers,
including
homocysteine,
insulin
ferritin,
suggesting
multifaceted
neurobiological
basis
syndrome.
These
findings
offer
insights
into
underlying
pathophysiology
MBI,
connection
symptoms
progression
AD.
narrative
review,
we
aim
summarize
critically
discuss
emerging
literature
evidence
linking
biomarkers,
hoping
shed
more
on
MBI's
pathophysiology,
its
AD-related
neurobiology,
practical
utility
predicting
impairment,
guiding
interventions
managing
risk
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
Role of Antioxidants in Modulating the Microbiota–Gut–Brain Axis and Their Impact on Neurodegenerative Diseases
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3658 - 3658
Опубликована: Апрель 12, 2025
This
narrative
review
presents
the
role
of
antioxidants
in
regulating
gut
microbiota
and
impact
on
gut–brain
axis,
with
a
particular
focus
neurodegenerative
diseases,
such
as
Alzheimer’s
(AD)
Parkinson’s
disease
(PD).
These
diseases
are
characterised
by
cognitive
decline,
motor
dysfunction,
neuroinflammation,
all
which
significantly
exacerbated
oxidative
stress.
elucidates
contribution
damage
to
progression
explores
potential
mitigate
these
pathological
processes
through
modulation
associated
pathways.
Based
recent
studies
retrieved
from
reputable
databases,
including
PubMed,
Web
Science,
Scopus,
this
article
outlines
mechanisms
influence
health
exert
neuroprotective
effects.
Specifically,
it
discusses
how
antioxidants,
polyphenols,
vitamins,
flavonoids,
contribute
reduction
reactive
oxygen
species
(ROS)
production
thereby
promoting
neuronal
survival
minimising
brain.
In
addition,
modulating
key
molecular
pathways
involved
stress
NF-κB,
Nrf2,
MAPK,
PI3K/AKT
pathways,
regulate
ROS
generation,
inflammatory
cytokine
expression,
antioxidant
responses
essential
for
maintaining
cellular
homeostasis
both
central
nervous
system.
complex
relationship
between
gut-derived
metabolites,
stress,
highlighting
dysbiosis—an
imbalance
microbiota—can
exacerbate
accelerating
AD
PD.
The
also
examines
short-chain
fatty
acids
(SCFAs)
produced
beneficial
bacteria
attenuate
neuroinflammation
damage.
Furthermore,
therapeutic
microbiota-targeted
interventions,
delivery
probiotics
prebiotics,
innovative
strategies
restore
microbial
support
brain
health.
By
synthesising
current
knowledge
interplay
underlying
neurodegeneration,
highlights
promise
antioxidant-based
interventions
mitigating
progression.
It
need
further
research
into
antioxidant-rich
dietary
microbiota-focused
therapies
promising
avenues
prevention
treatment
diseases.
Язык: Английский
Key genes and pathways in asparagine metabolism in Alzheimer’s Disease: a bioinformatics approach
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 28, 2025
Abstract
Background
Asparagine
(Asn)
metabolism
is
essential
for
maintaining
cellular
homeostasis
and
supporting
neuronal
energy
demands.
Recent
studies
have
suggested
its
dysregulation
may
contribute
to
Alzheimer’s
disease
(AD)
pathogenesis;
however,
the
specific
genes
regulatory
mechanisms
involved
remain
incompletely
understood.
Methods
Four
publicly
available
microarray
datasets
(GSE5281,
GSE29378,
GSE36980,
GSE138260)
were
utilized
investigate
with
differential
expression
between
control
AD
samples.
metabolism-related
(AMGs)
retrieved
from
GeneCards
database,
their
intersection
DEGs
yielded
candidate
asparagine
differentially
expressed
(AMG-DEGs).
Functional
enrichment
analysis
(Gene
Set
Enrichment
Analysis,
Gene
Ontology
Kyoto
Encyclopedia
of
Genes
Genomes),
protein–protein
interaction
(PPI)
network
analysis,
centrality
scoring
identified
hub
genes.
Regulatory
investigated
through
construction
competing
endogenous
RNA
transcription
factor
networks.
Potential
therapeutic
compounds
predicted
via
drug–gene
evaluated
using
molecular
docking
simulations.
Results
Thirty-nine
AMG-DEGs
found
be
enriched
in
neurodevelopmental,
synaptic
transmission,
inflammatory
signaling
pathways.
PPI
screening
revealed
seven
(
HPRT1
,
GAD2
TUBB3
GFAP
CD44
CCL2
NFKBIA
).
highlighted
miRNAs,
long
non-coding
RNAs,
factors
modulation.
Drug
Bathocuproine
disulfonate,
DL-Mevalonic
acid,
Phenethyl
isothiocyanate
as
promising
strong
binding
affinities
proteins.
Conclusion
This
study
comprehensively
maps
reveals
a
set
elements
potentially
progression.
The
provide
foundation
further
experimental
validation
development
novel
metabolism-targeted
strategies
treatment.
Язык: Английский
Integrating genetic and immune profiles for personalized immunotherapy in Alzheimer’s disease
Frontiers in Medicine,
Год журнала:
2025,
Номер
12
Опубликована: Июнь 2, 2025
Alzheimer’s
disease
(AD)
is
the
most
frequent
cause
of
dementia
worldwide,
and
it
estimated
that
number
patients
will
increase
to
131
million
by
2050.
Most
current
methods
dealing
with
AD
are
designed
alleviate
symptoms,
there
no
effective
way
stopping
progression
disease.
Personalized
immunotherapy
has
potential
be
highly
cut
down
on
side
effects
because
can
targeted
accurately
intervened
early.
Considering
genetic
factors,
many
studies
increasingly
looking
at
taking
immune
status
into
account.
This
article
further
discusses
characteristics
AD,
integrating
multiple
histological
data,
identification
biomarkers,
stratification
patients,
precise
treatment
plans,
application
future
trends
immunotherapy,
giving
new
directions
for
AD.
In
this
mini-review,
authors
address
critical
role
background
play
in
shaping
therapeutic
strategies
noting
a
unique
response
carriers
APOEε4
allele
compared
non-carriers,
difference
may
affect
course
as
well
efficacy
immunotherapy.
The
aim
review
give
an
overview
understanding
influence
factors
each
other
focusing
impact
its
implications
Язык: Английский