Cold Spring Harbor Perspectives in Biology,
Journal Year:
2024,
Volume and Issue:
16(7), P. a041356 - a041356
Published: Feb. 5, 2024
In
addition
to
their
many
functions
in
the
healthy
central
nervous
system
(CNS),
astrocytes
respond
CNS
damage
and
disease
through
a
process
called
"reactivity."
Recent
evidence
reveals
that
astrocyte
reactivity
is
heterogeneous
spectrum
of
potential
changes
occur
context-specific
manner.
These
are
determined
by
diverse
signaling
events
vary
not
only
with
nature
severity
different
insults
but
also
location
CNS,
genetic
predispositions,
age,
potentially
"molecular
memory"
previous
events.
Astrocyte
can
be
associated
both
essential
beneficial
as
well
harmful
effects.
The
available
information
rapidly
expanding
much
has
been
learned
about
molecular
diversity
reactivity.
Emerging
functional
associations
point
toward
roles
for
determining
outcome
disorders.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: April 6, 2023
The
system
physiology
approaches
that
emerge
in
western
countries
recent
years
echo
the
holistic
view
of
ancient
Traditional
Chinese
Medicine
(TCM)
practices
deal
with
root,
rather
than
only
symptoms
diseases.
Particularly,
TCM
practices,
including
acupuncture,
emphasize
mobilization
self-healing
mechanisms
to
bring
back
body
homeostasis.
Acupuncture
has
been
practiced
for
over
two
thousand
modulate
via
stimulation
at
specific
regions
(acupoints).
With
development
various
research
on
acupuncture
therapy,
its
regulatory
effect
immune
gradually
recognized,
especially
immunological
diseases,
infectious
and
allergic
In
this
study,
we
reviewed
immunomodulatory
mechanism
systematically
integrates
existing
respectively
elucidate
modulatory
innate
system,
adaptive
well-known
neuroanatomical
mechanisms,
intact
somatosensory-autonomic
reflex
pathway.
advances
made
systems
studies,
now
have
a
great
opportunity
gain
insight
into
how
modulates
immunity,
subsequently
improves
efficacy.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Oct. 19, 2023
Abstract
The
recent
success
of
mRNA
therapeutics
against
pathogenic
infections
has
increased
interest
in
their
use
for
other
human
diseases
including
cancer.
However,
the
precise
delivery
genetic
cargo
to
cells
and
tissues
remains
challenging.
Here,
we
show
an
adaptive
strategy
that
enables
docking
different
targeting
ligands
onto
surface
mRNA-loaded
small
extracellular
vesicles
(sEVs).
This
is
achieved
by
using
a
microfluidic
electroporation
approach
which
combination
nano-
milli-second
pulses
produces
large
amounts
IFN-γ
sEVs
with
CD64
overexpressed
on
surface.
molecule
serves
as
adaptor
dock
ligands,
such
anti-CD71
anti-programmed
cell
death-ligand
1
(PD-L1)
antibodies.
resulting
immunogenic
(imsEV)
preferentially
target
glioblastoma
generate
potent
antitumour
activities
vivo,
tumours
intrinsically
resistant
immunotherapy.
Together,
these
results
provide
engineering
functionality
pave
way
adoption
cancer
immunotherapy
applications.
Glia,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 3, 2025
ABSTRACT
Reactive
astrocytes
are
associated
with
Alzheimer's
disease
(AD),
and
several
AD
genetic
risk
variants
genes
highly
expressed
in
astrocytes.
However,
the
contribution
of
within
to
cellular
processes
relevant
pathogenesis
remains
ill‐defined.
Here,
we
present
a
resource
for
studying
using
large
collection
induced
pluripotent
stem
cell
(iPSC)
lines
from
deeply
phenotyped
individuals
range
neuropathological
cognitive
outcomes.
IPSC
44
were
differentiated
into
followed
by
unbiased
molecular
profiling
RNA
sequencing
tandem
mass
tag‐mass
spectrometry.
We
demonstrate
utility
this
examining
gene‐
pathway‐level
associations
clinical
traits,
as
well
analyzing
resilience
factors
through
parallel
analyses
iPSC‐astrocytes
brain
tissue
same
individuals.
Our
reveal
that
pathways
altered
iPSC‐derived
concordantly
dysregulated
tissue.
This
includes
increased
levels
prefoldin
proteins,
extracellular
matrix
factors,
COPI‐mediated
trafficking
components
reduced
proteins
involved
respiration
fatty
acid
oxidation.
Additionally,
resilient
high
neuropathology
show
elevated
basal
interferon
response
secretion
gamma.
Correspondingly,
higher
polygenic
scores
lower
study
establishes
an
experimental
system
integrates
information
matched
iPSC
data
cohort
identify
contributions
affecting
resilience.
Molecular Neurodegeneration,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: March 31, 2025
Abstract
Immune
mechanisms
play
a
fundamental
role
in
Alzheimer’s
disease
(AD)
pathogenesis,
suggesting
that
approaches
which
target
immune
cells
and
immunologically
relevant
molecules
can
offer
therapeutic
opportunities
beyond
the
recently
approved
amyloid
beta
monoclonal
therapies.
In
this
review,
we
provide
an
overview
of
immunomodulatory
therapeutics
development,
including
their
preclinical
evidence
clinical
trial
results.
Along
with
detailing
processes
involved
AD
pathogenesis
highlighting
how
these
be
therapeutically
targeted
to
modify
progression,
summarize
knowledge
gained
from
previous
trials
immune-based
interventions,
series
recommendations
for
development
future
treat
AD.
Glia,
Journal Year:
2021,
Volume and Issue:
70(1), P. 5 - 19
Published: Aug. 31, 2021
Abstract
Astrocytes
are
glial
cells
that
support
neurological
function
in
the
central
nervous
system
(CNS),
part,
by
providing
structural
for
neuronal
synapses
and
blood
vessels,
participating
electrical
chemical
transmission,
trophic
via
soluble
factors.
Dysregulation
of
astrocyte
contributes
to
decline
CNS
diseases.
Neurological
diseases
highly
heterogeneous
but
share
common
features
cellular
stress
including
accumulation
misfolded
proteins.
Endoplasmic
reticulum
(ER)
has
been
reported
nearly
all
neurodegenerative
ER
occurs
when
there
is
an
proteins
lumen
protein
folding
demand
overwhelmed.
initiates
unfolded
response
(UPR)
restore
homeostasis
abating
translation
and,
if
cell
irreparably
damaged,
initiating
apoptosis.
Although
aggregation
misfolding
disease
well
described,
cell‐specific
contributions
UPR
physiological
states
poorly
understood.
Recent
work
revealed
a
role
active
signaling
may
drive
astrocytes
toward
maladaptive
phenotype
various
model
systems.
In
stress,
produce
inflammatory
mediators,
have
reduced
support,
can
transmit
other
cells.
This
review
will
discuss
current
known
consequences
activated
astrocytes.
Cancer Discovery,
Journal Year:
2022,
Volume and Issue:
12(5), P. 1314 - 1335
Published: March 9, 2022
Abstract
Brain
metastasis
is
a
significant
cause
of
morbidity
and
mortality
in
multiple
cancer
types
represents
an
unmet
clinical
need.
The
mechanisms
that
mediate
metastatic
growth
the
brain
parenchyma
are
largely
unknown.
Melanoma,
which
has
highest
rate
among
common
types,
ideal
model
to
study
how
cells
adapt
parenchyma.
Our
unbiased
proteomics
analysis
melanoma
short-term
cultures
revealed
proteins
implicated
neurodegenerative
pathologies
differentially
expressed
explanted
from
metastases
compared
with
those
derived
extracranial
metastases.
We
showed
require
amyloid
beta
(Aβ)
for
survival
Melanoma-secreted
Aβ
activates
surrounding
astrocytes
prometastatic,
anti-inflammatory
phenotype
prevents
phagocytosis
by
microglia.
Finally,
we
demonstrate
pharmacologic
inhibition
decreases
burden.
Significance:
results
reveal
novel
mechanistic
connection
between
Alzheimer's
disease,
two
previously
unrelated
pathologies;
establish
as
promising
therapeutic
target
metastasis;
suppression
neuroinflammation
critical
feature
adaptation
This
article
highlighted
In
Issue
feature,
p.
1171
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
12
Published: Jan. 10, 2022
Neuronal
death
and
inflammatory
response
are
two
common
pathological
hallmarks
of
acute
central
nervous
system
injury
chronic
degenerative
disorders,
both
which
closely
related
to
cognitive
motor
dysfunction
associated
with
various
neurological
diseases.
Neurological
diseases
highly
heterogeneous;
however,
they
share
a
pathogenesis,
that
is,
the
aberrant
accumulation
misfolded/unfolded
proteins
within
endoplasmic
reticulum
(ER).
Fortunately,
cell
has
intrinsic
quality
control
mechanisms
maintain
proteostasis
network,
such
as
chaperone-mediated
folding
ER-associated
degradation.
However,
when
these
fail,
accumulate
in
ER
lumen
contribute
stress.
stress
been
implicated
nearly
all
initiates
unfolded
protein
restore
proteostasis,
if
damage
is
irreversible,
it
elicits
intracellular
cascades
inflammation.
With
growing
appreciation
functional
association
between
improved
understanding
multiple
underlying
molecular
mechanisms,
pharmacological
genetic
targeting
beginning
emerge
therapeutic
approaches
for
Annual Review of Immunology,
Journal Year:
2022,
Volume and Issue:
40(1), P. 143 - 167
Published: Jan. 6, 2022
The
gut
microbiome
influences
many
host
physiologies,
spanning
gastrointestinal
function,
metabolism,
immune
homeostasis,
neuroactivity,
and
behavior.
Many
microbial
effects
on
the
are
orchestrated
by
bidirectional
interactions
between
system.
Imbalances
in
this
dialogue
can
lead
to
dysfunction
immune-mediated
conditions
distal
organs
including
brain.
Dysbiosis
of
dysregulated
neuroimmune
responses
common
comorbidities
neurodevelopmental,
neuropsychiatric,
neurological
disorders,
highlighting
importance
microbiome-neuroimmune
axis
as
a
regulator
central
nervous
system
homeostasis.
In
review,
we
discuss
recent
evidence
supporting
role
for
regulating
landscape
health
disease.