Cell,
Год журнала:
2024,
Номер
187(19), С. 5336 - 5356.e30
Опубликована: Авг. 12, 2024
Tumors
growing
in
metabolically
challenged
environments,
such
as
glioblastoma
the
brain,
are
particularly
reliant
on
crosstalk
with
their
tumor
microenvironment
(TME)
to
satisfy
high
energetic
needs.
To
study
intricacies
of
this
metabolic
interplay,
we
interrogated
heterogeneity
TME
using
single-cell
and
multi-omics
analyses
identified
rewired
tumor-associated
macrophage
(TAM)
subpopulations
pro-tumorigenic
properties.
These
TAM
subsets,
termed
lipid-laden
macrophages
(LLMs)
reflect
cholesterol
accumulation,
epigenetically
rewired,
display
immunosuppressive
features,
enriched
aggressive
mesenchymal
subtype.
Engulfment
cholesterol-rich
myelin
debris
endows
subsets
TAMs
acquire
an
LLM
phenotype.
Subsequently,
LLMs
directly
transfer
myelin-derived
lipids
cancer
cells
LXR/Abca1-dependent
manner,
thereby
fueling
heightened
demands
glioblastoma.
Our
work
provides
in-depth
understanding
immune-metabolic
interplay
during
progression,
laying
a
framework
unveil
targetable
vulnerabilities
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Сен. 22, 2023
Abstract
Microglia
activation
is
observed
in
various
neurodegenerative
diseases.
Recent
advances
single-cell
technologies
have
revealed
that
these
reactive
microglia
were
with
high
spatial
and
temporal
heterogeneity.
Some
identified
specific
states
correlate
pathological
hallmarks
are
associated
functions.
both
exert
protective
function
by
phagocytosing
clearing
protein
aggregates
play
detrimental
roles
due
to
excessive
uptake
of
aggregates,
which
would
lead
microglial
phagocytic
ability
impairment,
neuroinflammation,
eventually
neurodegeneration.
In
addition,
peripheral
immune
cells
infiltration
shapes
into
a
pro-inflammatory
phenotype
accelerates
disease
progression.
also
act
as
mobile
vehicle
propagate
aggregates.
Extracellular
vesicles
released
from
autophagy
impairment
all
contribute
progression
Thus,
enhancing
phagocytosis,
reducing
microglial-mediated
inhibiting
exosome
synthesis
secretion,
promoting
conversion
considered
be
promising
strategies
for
the
therapy
Here
we
comprehensively
review
biology
diseases,
including
Alzheimer’s
disease,
Parkinson’s
multiple
system
atrophy,
amyotrophic
lateral
sclerosis,
frontotemporal
dementia,
progressive
supranuclear
palsy,
corticobasal
degeneration,
dementia
Lewy
bodies
Huntington’s
disease.
We
summarize
possible
microglia-targeted
interventions
treatments
against
diseases
preclinical
clinical
evidence
cell
experiments,
animal
studies,
trials.
Nature,
Год журнала:
2023,
Номер
620(7973), С. 374 - 380
Опубликована: Авг. 2, 2023
Low-grade
inflammation
is
a
hallmark
of
old
age
and
central
driver
ageing-associated
impairment
disease1.
Multiple
factors
can
contribute
to
inflammation2;
however,
the
molecular
pathways
that
transduce
aberrant
inflammatory
signalling
their
impact
in
natural
ageing
remain
unclear.
Here
we
show
cGAS-STING
pathway,
which
mediates
immune
sensing
DNA3,
critical
chronic
functional
decline
during
ageing.
Blockade
STING
suppresses
phenotypes
senescent
human
cells
tissues,
attenuates
ageing-related
multiple
peripheral
organs
brain
mice,
leads
an
improvement
tissue
function.
Focusing
on
brain,
reveal
activation
triggers
reactive
microglial
transcriptional
states,
neurodegeneration
cognitive
decline.
Cytosolic
DNA
released
from
perturbed
mitochondria
elicits
cGAS
activity
microglia,
defining
mechanism
by
engaged
brain.
Single-nucleus
RNA-sequencing
analysis
microglia
hippocampi
gain-of-function
mouse
model
demonstrates
engagement
sufficient
direct
states
leading
bystander
cell
inflammation,
neurotoxicity
impaired
memory
capacity.
Our
findings
establish
pathway
as
blockade
potential
strategy
halt
neurodegenerative
processes
age.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 16, 2024
Abstract
The
human
gastrointestinal
tract
is
populated
with
a
diverse
microbial
community.
vast
genetic
and
metabolic
potential
of
the
gut
microbiome
underpins
its
ubiquity
in
nearly
every
aspect
biology,
including
health
maintenance,
development,
aging,
disease.
advent
new
sequencing
technologies
culture-independent
methods
has
allowed
researchers
to
move
beyond
correlative
studies
toward
mechanistic
explorations
shed
light
on
microbiome–host
interactions.
Evidence
unveiled
bidirectional
communication
between
central
nervous
system,
referred
as
“microbiota–gut–brain
axis”.
microbiota–gut–brain
axis
represents
an
important
regulator
glial
functions,
making
it
actionable
target
ameliorate
development
progression
neurodegenerative
diseases.
In
this
review,
we
discuss
mechanisms
As
provides
essential
cues
microglia,
astrocytes,
oligodendrocytes,
examine
communications
microbiota
these
cells
during
healthy
states
Subsequently,
diseases
using
metabolite-centric
approach,
while
also
examining
role
microbiota-related
neurotransmitters
hormones.
Next,
targeting
intestinal
barrier,
blood–brain
meninges,
peripheral
immune
system
counteract
dysfunction
neurodegeneration.
Finally,
conclude
by
assessing
pre-clinical
clinical
evidence
probiotics,
prebiotics,
fecal
transplantation
A
thorough
comprehension
will
foster
effective
therapeutic
interventions
for
management
Annual Review of Pathology Mechanisms of Disease,
Год журнала:
2021,
Номер
17(1), С. 121 - 139
Опубликована: Окт. 4, 2021
Multiple
sclerosis
(MS)
is
a
chronic
autoimmune,
inflammatory,
and
neurodegenerative
disease
that
affects
the
central
nervous
system
(CNS).
MS
characterized
by
immune
dysregulation,
which
results
in
infiltration
of
CNS
cells,
triggering
demyelination,
axonal
damage,
neurodegeneration.
Although
exact
causes
are
not
fully
understood,
genetic
environmental
factors
thought
to
control
onset
progression.
In
this
article,
we
review
main
immunological
mechanisms
involved
pathogenesis.
