Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Окт. 29, 2024
Abstract
Background
Persistent
innate
and
adaptive
immune
responses
in
the
brain
contribute
to
progression
of
Alzheimer’s
disease
(AD).
APOE4
,
most
important
genetic
risk
factor
for
sporadic
AD,
encodes
apolipoprotein
E4,
which
by
itself
is
a
potent
modulator
response.
However,
little
known
about
hub
that
governs
crosstalk
between
nervous
systems.
Transient
receptor
potential
vanilloid
type
1
(TRPV1)
channel
ligand-gated,
nonselective
cation
with
Ca
2+
permeability,
has
been
proposed
as
neuroprotective
target
AD.
Methods
Using
-sensitive
dyes,
dynamic
changes
microglia
were
measured,
including
exogenous
uptake
endoplasmic
reticulum
release.
The
mRFP-GFP-tagged
LC3
plasmid
was
expressed
characterize
role
TRPV1
autophagic
flux.
Transcriptomic
analyses
flow
cytometry
performed
investigate
effects
on
T
cells
from
APOE
-targeted
replacement
mice
microglia-specific
gene
deficiency.
Results
Both
derived
induced
pluripotent
stem
AD
patients
-related
tauopathy
mouse
model
showed
significantly
increased
cholesterol
biosynthesis
accumulation
compared
their
APOE3
counterparts.
Further,
dysregulation
associated
persistent
activation
elevation
major
histocompatibility
complex
II-dependent
antigen
presentation
microglia,
subsequently
accompanied
cell
infiltration.
In
addition,
TRPV1-mediated
transient
influx
mitigated
suppressing
transcriptional
sterol
regulatory
element-binding
protein
2,
promoted
activity
reduced
lysosomal
accumulation,
sufficient
resolve
excessive
response
neurodegeneration
model.
Moreover,
deficiency
accelerated
glial
inflammation,
an
Conclusions
findings
provide
new
perspectives
treatment
-dependent
Cells,
Год журнала:
2023,
Номер
12(24), С. 2824 - 2824
Опубликована: Дек. 12, 2023
The
greatest
risk
factor
for
neurodegeneration
is
the
aging
of
multiple
cell
types
human
CNS,
among
which
microglia
are
important
because
they
"sentinels"
internal
and
external
perturbations
have
long
lifespans.
We
aim
to
emphasize
microglial
signatures
in
physiologic
brain
Alzheimer's
disease
(AD).
A
systematic
literature
search
all
published
articles
about
senescence
healthy
AD
was
performed,
searching
PubMed
Scopus
online
databases.
Among
1947
screened,
a
total
289
were
assessed
full-text
eligibility.
Microglial
transcriptomic,
phenotypic,
neuropathological
profiles
analyzed
comprising
AD.
Our
review
highlights
that
studies
on
animal
models
only
partially
clarify
what
happens
humans.
Human
mice
hugely
heterogeneous.
Like
two-sided
coin,
can
be
protective
or
harmful,
depending
context.
Brain
health
depends
upon
balance
between
actions
reactions
maintaining
homeostasis
cooperation
with
other
(especially
astrocytes
oligodendrocytes).
During
aging,
accumulating
oxidative
stress
mitochondrial
dysfunction
weaken
leading
dystrophic/senescent,
otherwise
over-reactive,
phenotype-enhancing
neurodegenerative
phenomena.
Microglia
crucial
managing
Aβ,
pTAU,
damaged
synapses,
being
pivotal
pathogenesis.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 15, 2024
Abstract
The
Alzheimer’s
disease
(AD)
human
genetic
landscape
indicates
microglia
are
an
important
cell
type
in
the
brain
that
modifies
risk.
A
common
loss-of-functon(LOF)
coding
variant
paired
immunoglobulin-like
2
receptor
alpha
(PILRA)
is
associated
with
reduced
risk
of
AD,
however
mechanisms
underlying
this
protective
effect
poorly
defined.
Here
we
identify
biological
functions
PILRA,
immunoreceptor
tyrosine-based
inhibitory
motif
(ITIM)-containing
receptor,
iPSC-derived
and
chimeric
mice.
CRISPR-mediated
PILRA
knockout
(KO)
increase
ApoE
uptake
lipid
droplet
formation
concomitant
proinflammatory
lipids
metabolites
increased
antioxidant
lipids.
Despite
droplets,
KO
exhibit
improved
mitochondrial
function,
lysosomal
degradation,
enhanced
migration,
reactive
oxygen
species,
significantly
attenuated
cytokine
responses
to
stimuli.
In
addition,
found
mediates
downstream
effects
via
STAT1/3
signaling.
Single
RNA-sequencing
isolated
from
AD
mice
showed
similar
pathways
were
regulated
a
context.
Finally,
antagonist
antibody
phenocopies
LOF.
Together,
these
findings
define
inhibition
as
therapeutic
approach
modulate
microglial
immunometabolism,
thus
identifying
pharmacologically
tractable
target
for
AD.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
175, С. 116519 - 116519
Опубликована: Апрель 24, 2024
To
elucidate
the
therapeutic
effects
and
mechanisms
of
Atractylodes
macrocephala
extract
crystallize
(BZEP)
BZEP
self-microemulsion
(BZEPWR)
on
metabolic
dysfunction-associated
fatty
liver
disease
(MAFLD)
induced
by
"high
sugar,
high
fat,
excessive
alcohol
consumption"
based
gut-liver
axis
HDL/LPS
signaling
pathway.
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Авг. 21, 2024
Introduction
Alzheimer’s
disease
(AD),
a
major
cause
of
dementia
globally,
imposes
significant
societal
and
personal
costs.
This
review
explores
the
efficacy
physical
exercise
as
non-pharmacological
intervention
to
mitigate
impacts
AD.
Methods
draws
on
recent
studies
that
investigate
effects
neuroinflammation
neuronal
enhancement
in
individuals
with
Results
Consistent
alters
neuroinflammatory
pathways,
enhances
cognitive
functions,
bolsters
brain
health
among
AD
patients.
It
favorably
influences
activation
states
microglia
astrocytes,
fortifies
integrity
blood-brain
barrier,
attenuates
gut
inflammation
associated
These
changes
are
substantial
improvements
performance
indicators.
Discussion
The
findings
underscore
potential
integrating
into
comprehensive
management
strategies.
Emphasizing
necessity
for
further
research,
this
advocates
refinement
regimens
maximize
their
enduring
benefits
decelerating
progression
Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Окт. 29, 2024
Abstract
Background
Persistent
innate
and
adaptive
immune
responses
in
the
brain
contribute
to
progression
of
Alzheimer’s
disease
(AD).
APOE4
,
most
important
genetic
risk
factor
for
sporadic
AD,
encodes
apolipoprotein
E4,
which
by
itself
is
a
potent
modulator
response.
However,
little
known
about
hub
that
governs
crosstalk
between
nervous
systems.
Transient
receptor
potential
vanilloid
type
1
(TRPV1)
channel
ligand-gated,
nonselective
cation
with
Ca
2+
permeability,
has
been
proposed
as
neuroprotective
target
AD.
Methods
Using
-sensitive
dyes,
dynamic
changes
microglia
were
measured,
including
exogenous
uptake
endoplasmic
reticulum
release.
The
mRFP-GFP-tagged
LC3
plasmid
was
expressed
characterize
role
TRPV1
autophagic
flux.
Transcriptomic
analyses
flow
cytometry
performed
investigate
effects
on
T
cells
from
APOE
-targeted
replacement
mice
microglia-specific
gene
deficiency.
Results
Both
derived
induced
pluripotent
stem
AD
patients
-related
tauopathy
mouse
model
showed
significantly
increased
cholesterol
biosynthesis
accumulation
compared
their
APOE3
counterparts.
Further,
dysregulation
associated
persistent
activation
elevation
major
histocompatibility
complex
II-dependent
antigen
presentation
microglia,
subsequently
accompanied
cell
infiltration.
In
addition,
TRPV1-mediated
transient
influx
mitigated
suppressing
transcriptional
sterol
regulatory
element-binding
protein
2,
promoted
activity
reduced
lysosomal
accumulation,
sufficient
resolve
excessive
response
neurodegeneration
model.
Moreover,
deficiency
accelerated
glial
inflammation,
an
Conclusions
findings
provide
new
perspectives
treatment
-dependent
