Transfer
RNA-derived
small
RNAs,
a
recently
identified
class
of
noncoding
play
crucial
role
in
regulating
gene
expression
and
are
implicated
cerebrovascular
diseases.
However,
the
specific
biological
roles
mechanisms
transfer
RNAs
intracranial
aneurysms
(IAs)
remain
unclear.
In
this
study,
we
that
RNA-Asp-GTC
derived
fragment
(tRF-AspGTC)
is
highly
expressed
IA
tissues
both
humans
mice.
tRF-AspGTC
promotes
formation
by
facilitating
phenotypic
switching
vascular
smooth
muscle
cells,
increasing
matrix
metalloproteinase
9
expression,
inducing
oxidative
stress
inflammatory
responses.
Mechanistically,
binds
to
galectin-3,
inhibiting
tripartite
motif
29-mediated
ubiquitination
stabilizing
galectin-3.
This
stabilization
activates
toll-like
receptor
4/MyD88/nuclear
factor
kappa
B
pathway,
further
driving
inflammation.
Clinically,
circulating
exosomal
demonstrates
strong
diagnostic
efficacy
for
IAs
as
an
independent
risk
occurrence.
These
findings
highlight
potential
promising
biomarker
therapeutic
target
IAs.
Journal of Neuroinflammation,
Journal Year:
2022,
Volume and Issue:
19(1)
Published: Nov. 17, 2022
Abstract
Microglia
represent
the
first
line
of
immune
feedback
in
brain.
Beyond
surveillance,
they
are
essential
for
maintaining
brain
homeostasis.
Recent
research
has
revealed
microglial
cells'
spatiotemporal
heterogeneity
based
on
their
local
and
time-based
functions
trauma
or
disease
when
homeostasis
is
disrupted.
Distinct
"microglial
signatures"
have
been
recorded
physiological
states
injuries,
with
discrete
sometimes
overlapping
pro-
anti-inflammatory
functions.
involved
neurological
repair
processes,
such
as
neurovascular
unit
restoration
synaptic
plasticity,
manage
extent
damage
due
to
phenotype
switching.
The
versatility
cellular
phenotypes
beyond
classical
M1/M2
classification,
well
double-edge
actions
microglia
neurodegeneration,
indicate
need
further
exploration
cell
dynamics
contribution
neurodegenerative
processes.
This
review
discusses
homeostatic
different
subsets
focusing
neuropathological
conditions.
Also,
we
address
feasibility
targeting
a
therapeutic
strategy
diseases.
Molecular Neurodegeneration,
Journal Year:
2022,
Volume and Issue:
17(1)
Published: Dec. 17, 2022
Amongst
risk
alleles
associated
with
late-onset
Alzheimer's
disease
(AD),
those
that
converged
on
the
regulation
of
microglia
activity
have
emerged
as
central
to
progression.
Yet,
how
canonical
amyloid-β
(Aβ)
and
tau
pathologies
regulate
subtypes
during
progression
AD
remains
poorly
understood.We
use
single-cell
RNA-sequencing
profile
from
mice
exhibiting
both
Aβ
across
We
identify
novel
are
induced
in
response
a
disease-stage-specific
manner.
To
validate
observation
mouse
models,
we
also
generated
snRNA-Seq
dataset
human
superior
frontal
gyrus
(SFG)
entorhinal
cortex
(ERC)
at
different
Braak
stages.We
show
early-stage
disease,
interferon
signaling
induces
subtype
termed
Early-stage
AD-Associated
Microglia
(EADAM)
pathologies.
During
late-stage
second
Late-stage
(LADAM)
is
detected.
While
similar
observed
other
models
neurodegenerative
magnitude
composition
gene
signatures
found
EADAM
LADAM
distinct,
suggesting
necessity
elicit
their
emergence.
Importantly,
pattern
EADAM-
LADAM-associated
expression
brains,
early
(Braak
II)-
or
late
VI/V)-
stage
respectively.
Furthermore,
several
Siglec
genes
selectively
expressed
either
LADAM.
Siglecg
white-matter-associated
LADAM,
Siglec-10,
orthologue
Siglecg,
progressively
elevated
an
AD-stage-dependent
manner
but
not
shown
non-AD
tauopathy.Using
scRNA-Seq
bearing
and/or
pathologies,
by
combination
stage-specific
Our
findings
suggest
required
for
induction
In
addition,
revealed
Siglecs
biomarkers
potential
therapeutic
targets.
Frontiers in Pharmacology,
Journal Year:
2023,
Volume and Issue:
14
Published: June 2, 2023
Despite
extensive
research,
no
disease-modifying
therapeutic
option,
able
to
prevent,
cure
or
halt
the
progression
of
Alzheimer’s
disease
[AD],
is
currently
available.
AD,
a
devastating
neurodegenerative
pathology
leading
dementia
and
death,
characterized
by
two
pathological
hallmarks,
extracellular
deposits
amyloid
beta
(Aβ)
intraneuronal
neurofibrillary
tangles
(NFTs)
consisting
altered
hyperphosphorylated
tau
protein.
Both
have
been
widely
studied
pharmacologically
targeted
for
many
years,
without
significant
results.
In
2022,
positive
data
on
monoclonal
antibodies
targeting
Aβ,
donanemab
lecanemab,
followed
2023
FDA
accelerated
approval
lecanemab
publication
final
results
phase
III
Clarity
AD
study,
strengthened
hypothesis
causal
role
Aβ
in
pathogenesis
AD.
However,
magnitude
clinical
effect
elicited
drugs
limited,
suggesting
that
additional
mechanisms
may
contribute
disease.
Cumulative
studies
shown
inflammation
as
one
main
contributors
recognition
specific
neuroinflammation
synergic
with
NFTs
cascades.
The
present
review
provides
an
overview
investigational
are
trials.
Moreover,
their
action,
positioning
cascade
events
occur
brain
throughout
potential
benefit/limitation
strategy
discussed
highlighted
well.
addition,
latest
patent
requests
inflammation-targeting
therapeutics
be
developed
will
also
discussed.
The Journal of Experimental Medicine,
Journal Year:
2024,
Volume and Issue:
221(2)
Published: Jan. 16, 2024
Aducanumab,
an
anti-amyloid
immunotherapy
for
Alzheimer’s
disease,
efficiently
reduces
Aβ,
though
its
plaque
clearance
mechanisms,
long-term
effects,
and
effects
of
discontinuation
are
not
fully
understood.
We
assessed
the
effect
aducanumab
treatment
withdrawal
on
neuritic
dystrophy,
astrocytes,
microglia
in
APP/PS1
amyloid
mouse
model.
found
that
reductions
dystrophy
during
acute
were
accompanied
by
microglial
astrocytic
activation,
recruitment
to
plaques
adoption
aducanumab-specific
pro-phagocytic
pro-degradation
transcriptomic
signature,
indicating
a
role
aducanumab-mediated
Aβ
clearance.
Reductions
sustained
15
but
30
wk
after
discontinuation,
reaccumulation
coincided
with
loss
signature
failure
reactivate.
This
suggests
despite
initial
benefit
from
treatment,
unable
respond
later
restrain
reaccumulation,
making
further
studies
amyloid-directed
crucial
assessing
safety
efficacy.
Journal of Neuroinflammation,
Journal Year:
2025,
Volume and Issue:
22(1)
Published: April 18, 2025
Ischemic
stroke
triggers
a
cascade
of
pathological
events
that
affect
multiple
cell
types
and
often
lead
to
incomplete
functional
recovery.
Despite
advances
in
single-cell
technologies,
the
molecular
cellular
responses
contribute
long-term
post-stroke
impairment
remain
poorly
understood.
To
gain
better
insight
into
underlying
mechanisms,
we
generated
transcriptomic
atlas
from
distinct
brain
regions
using
mouse
model
permanent
focal
ischemia
at
one
month
post-injury.
Our
findings
reveal
cell-
region-specific
changes
within
stroke-injured
peri-infarct
tissue.
For
instance,
GABAergic
glutamatergic
neurons
exhibited
upregulated
genes
signaling
pathways
involved
axon
guidance
synaptic
plasticity,
downregulated
associated
with
aerobic
metabolism.
Using
cell-cell
communication
analysis,
identified
increased
strength
predicted
interactions
tissue
among
both
neural
non-neural
cells
via
such
as
those
involving
collagen,
protein
tyrosine
phosphatase
receptor,
neuronal
growth
regulator,
laminin,
several
adhesion
molecules.
Furthermore,
found
strong
correlation
between
transcriptome
after
observed
human
nonfatal
lesions.
Common
features
were
linked
inflammatory
responses,
extracellular
matrix
organization,
angiogenesis.
provide
detailed
resource
for
advancing
our
understanding
pathology
discovering
therapeutic
targets
repair
phase
Acta Neuropathologica,
Journal Year:
2023,
Volume and Issue:
146(1), P. 51 - 75
Published: May 18, 2023
Abstract
Parkinson’s
Disease
(PD)
is
a
neurodegenerative
and
progressive
disorder
characterised
by
intracytoplasmic
inclusions
called
Lewy
bodies
(LB)
degeneration
of
dopaminergic
neurons
in
the
substantia
nigra
(SN).
Aggregated
α-synuclein
(αSYN)
known
to
be
main
component
LB.
It
has
also
been
reported
interact
with
several
proteins
organelles.
Galectin-3
(GAL3)
have
detrimental
function
diseases.
galactose-binding
protein
without
catalytic
activity
expressed
mainly
activated
microglial
cells
central
nervous
system
(CNS).
GAL3
previously
found
outer
layer
LB
post-mortem
brains.
However,
role
PD
yet
elucidated.
In
samples,
we
identified
an
association
between
all
subjects
studied.
was
linked
less
αSYN
other
deposits,
including
pale
bodies.
associated
disrupted
lysosomes.
vitro
studies
demonstrate
that
exogenous
recombinant
Gal3
internalised
neuronal
cell
lines
primary
where
it
interacts
endogenous
αSyn
fibrils.
addition,
aggregation
experiments
show
affects
spatial
propagation
stability
pre-formed
fibrils
resulting
short,
amorphous
toxic
strains.
To
further
investigate
these
observations
vivo,
take
advantage
WT
Gal3KO
mice
subjected
intranigral
injection
adenovirus
overexpressing
human
as
model.
line
our
,
under
conditions,
genetic
deletion
leads
increased
intracellular
accumulation
within
remarkably
preserved
integrity
motor
function.
Overall,
data
suggest
prominent
for
process
formation,
leading
production
short
species
detriment
larger
strains
which
triggers
mouse
model
PD.