Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(17)
Published: April 18, 2024
DNA
damage
and
neurodegenerative
disorders
are
intimately
linked
but
the
underlying
mechanism
remains
elusive.
Here,
we
show
that
persistent
lesions
in
tissue-resident
macrophages
carrying
an
XPF-ERCC1
repair
defect
trigger
neuroinflammation
neuronal
cell
death
mice.
We
find
microglia
accumulate
dsDNAs
chromatin
fragments
cytosol,
which
sensed
thereby
stimulating
a
viral-like
immune
response
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Feb. 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
Cells,
Journal Year:
2022,
Volume and Issue:
11(13), P. 2091 - 2091
Published: June 30, 2022
Neuroinflammation
is
a
hallmark
of
many
neurodegenerative
diseases
(NDs)
and
plays
fundamental
role
in
mediating
the
onset
progression
disease.
Microglia,
which
function
as
first-line
immune
guardians
central
nervous
system
(CNS),
are
drivers
neuroinflammation.
Numerous
human
postmortem
studies
vivo
imaging
analyses
have
shown
chronically
activated
microglia
patients
with
various
acute
chronic
neuropathological
diseases.
While
microglial
activation
common
feature
NDs,
exact
pathological
states
complex
often
contradictory.
However,
there
consensus
that
play
biphasic
conditions,
detrimental
protective
phenotypes,
overall
response
different
phenotypes
depends
on
nature
duration
inflammatory
insult,
well
stage
disease
development.
This
review
provides
comprehensive
overview
current
research
responses
health,
aging,
special
emphasis
heterogeneous
phenotypic
such
hemorrhagic
stroke
(HS),
Alzheimer's
(AD),
Parkinson's
(PD).
The
primary
focus
translational
preclinical
animal
models
bulk/single-cell
transcriptome
samples.
Additionally,
this
covers
key
receptors
signaling
pathways
potential
therapeutic
targets
to
regulate
during
aging
NDs.
age-,
sex-,
species-specific
differences
will
be
briefly
reviewed.
Pharmacological Reviews,
Journal Year:
2022,
Volume and Issue:
75(1), P. 62 - 158
Published: Dec. 8, 2022
The
neurotransmitter
dopamine
is
a
key
factor
in
central
nervous
system
(CNS)
function,
regulating
many
processes
including
reward,
movement,
and
cognition.
Dopamine
also
regulates
critical
functions
peripheral
organs,
such
as
blood
pressure,
renal
activity,
intestinal
motility.
Beyond
these
functions,
growing
body
of
evidence
indicates
that
an
important
immunoregulatory
factor.
Most
types
immune
cells
express
receptors
other
dopaminergic
proteins,
take
up,
produce,
store,
and/or
release
dopamine,
suggesting
immunomodulation
for
function.
Targeting
pathways
could
be
promising
avenue
the
treatment
inflammation
disease,
but
despite
increasing
research
this
area,
data
on
specific
effects
disease
remain
inconsistent
poorly
understood.
Therefore,
review
integrates
current
knowledge
role
cell
function
inflammatory
signaling
across
systems.
We
discuss
understanding
regulation
CNS
tissues,
highlighting
diseases
Parkinson’s
several
neuropsychiatric
conditions,
neurologic
human
immunodeficiency
virus,
bowel
rheumatoid
arthritis,
others.
Careful
consideration
given
to
influence
experimental
design
results,
we
note
number
areas
need
further
research.
Overall,
our
immunology
at
cellular,
tissue,
level
prompts
development
therapeutics
strategies
targeted
toward
ameliorating
through
immunity.
Significance
Statement
Canonically,
recognized
involved
cognition,
reward.
However,
acts
modulator
periphery.
This
comprehensively
assesses
pathogenesis
cellular
tissue
level.
will
provide
broad
access
information
fields,
identify
investigation,
drive
therapeutic
strategies.
Biomedicine & Pharmacotherapy,
Journal Year:
2023,
Volume and Issue:
162, P. 114581 - 114581
Published: March 24, 2023
Puerarin
is
an
isoflavone
compound
derived
from
Pueraria
lobata
in
traditional
Chinese
medicine.
Accumulating
evidence
has
indicated
that
puerarin
demonstrates
multiple
pharmacological
effects
and
exhibits
treatment
potential
for
various
neurological
disorders.
Based
on
the
latest
research
progress
as
a
neuroprotective
agent,
its
activity,
molecular
mechanism,
therapeutic
application
were
systematically
reviewed
with
emphasis
pre-clinical
studies.
The
related
information
was
extracted
compiled
major
scientific
databases,
including
PubMed,
ScienceDirect,
SpringerLink,
National
Knowledge
Infrastructure,
using
'Puerarin',
'Neuroprotection',
'Apoptosis',
'Autophagy',
'Antioxidant',
'Mitochondria',
'Anti-inflammation'
keywords.
This
review
complied
Preferred
Reporting
Items
Systematic
Reviews
criteria.
Forty-three
articles
met
established
inclusion
exclusion
shown
against
variety
of
disorders,
ischemic
cerebrovascular
disease,
subarachnoid
hemorrhage,
epilepsy,
cognitive
traumatic
brain
injury,
Parkinson's
Alzheimer's
anxiety,
depression,
diabetic
neuropathy,
neuroblastoma/glioblastoma.
anti-apoptosis,
proinflammatory
mediator
inhibitory,
autophagy
regulatory,
anti-oxidative
stress,
mitochondria
protection,
Ca2+
influx
anti-neurodegenerative
activities.
exerts
noticeable
models
disorders
vivo
(animal).
will
contribute
to
development
novel
clinical
drug
candidate
However,
well-designed,
high-quality,
large-scale,
multicenter
randomized
studies
are
needed
determine
safety
utility
patients
Journal of Neuroinflammation,
Journal Year:
2023,
Volume and Issue:
20(1)
Published: Feb. 12, 2023
In
Parkinson's
disease
(PD),
neurotoxic
microglia,
Th1
cells,
and
Th17
cells
are
overactivated.
Overactivation
of
these
immune
exacerbates
the
process
leads
to
pathological
development
pro-inflammatory
cytokines,
chemokines,
contact-killing
compounds,
causing
loss
dopaminergic
neurons.
So
far,
we
have
mainly
focused
on
role
specific
class
in
PD
while
neglecting
impact
interactions
among
disease.
Therefore,
this
review
demonstrates
reciprocal
interplays
between
microglia
T
associated
subpopulations
through
cytokine
chemokine
production
that
impair
and/or
protect
PD.
Furthermore,
potential
targets
models
neuroinflammation
highlighted
provide
new
ideas/directions
for
future
research.
Frontiers in Neuroinformatics,
Journal Year:
2023,
Volume and Issue:
17
Published: Aug. 10, 2023
Quantification
of
microglial
activation
through
morphometric
analysis
has
long
been
a
staple
the
neuroimmunologist’s
toolkit.
Microglial
morphological
phenomics
can
be
conducted
either
manual
classification
or
constructing
digital
skeleton
and
extracting
data
from
it.
Multiple
open-access
paid
software
packages
are
available
to
generate
these
skeletons
via
semi-automated
and/or
fully
automated
methods
with
varying
degrees
accuracy.
Despite
advancements
in
morphometrics
(quantitative
measures
cellular
morphology),
there
limited
development
tools
analyze
datasets
they
generate,
particular
those
containing
parameters
tens
thousands
cells
analyzed
by
pipelines.
In
this
review,
we
compare
critique
approaches
using
cluster
machine
learning
driven
predictive
algorithms
that
have
developed
tackle
large
datasets,
propose
improvements
for
methods.
particular,
highlight
need
commitment
open
science
groups
developing
classifiers.
Furthermore,
call
attention
communication
between
strong
engineering/computer
background
neuroimmunologists
produce
effective
analytical
simplified
operability
if
see
their
wide-spread
adoption
glia
biology
community.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Jan. 6, 2023
Abstract
Amyotrophic
Lateral
Sclerosis
(ALS)
is
a
neurodegenerative
disease
with
poorly
understood
clinical
heterogeneity,
underscored
by
significant
differences
in
patient
age
at
onset,
symptom
progression,
therapeutic
response,
duration,
and
comorbidity
presentation.
We
perform
stratification
analysis
to
better
understand
the
variability
ALS
pathology,
utilizing
postmortem
frontal
motor
cortex
transcriptomes
derived
from
208
patients.
Building
on
emerging
role
of
transposable
element
(TE)
expression
ALS,
we
consider
locus-specific
TEs
as
distinct
molecular
features
during
stratification.
Here,
identify
three
unique
subtypes
this
cohort,
survival.
These
results
suggest
independent
mechanisms
drive
some
heterogeneity
ALS.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 23, 2024
Abstract
Microglia
nodules
(HLA-DR
+
cell
clusters)
are
associated
with
brain
pathology.
In
this
post-mortem
study,
we
investigated
whether
they
represent
the
first
stage
of
multiple
sclerosis
(MS)
lesion
formation.
We
show
that
microglia
more
severe
MS
Compared
to
in
stroke,
those
enhanced
expression
genes
previously
found
upregulated
lesions.
Furthermore,
lipid
metabolism,
presence
T
and
B
cells,
production
immunoglobulins
cytokines,
activation
complement
cascade,
metabolic
stress
MS.
frequently
phagocytose
oxidized
phospholipids
possess
a
tubular
mitochondrial
network.
Strikingly,
MS,
some
encapsulate
partially
demyelinated
axons.
Taken
together,
propose
by
cytokines
immunoglobulins,
together
phagocytosis
phospholipids,
may
lead
phenotype
prone
