Antioxidants,
Journal Year:
2024,
Volume and Issue:
13(9), P. 1072 - 1072
Published: Sept. 2, 2024
Frontotemporal
dementia
(FTD)
causes
progressive
neurodegeneration
in
the
frontal
and
temporal
lobes,
leading
to
behavioral,
cognitive,
language
impairments.
With
no
effective
treatment
available,
exploring
new
therapeutic
approaches
is
critical.
Recent
research
highlights
transcription
factor
Nuclear
Factor
erythroid-derived
2-like
2
(NRF2)
as
vital
limiting
neurodegeneration,
with
its
activation
shown
mitigate
FTD-related
processes
like
inflammation.
Dimethyl
fumarate
(DMF),
an
NRF2
activator,
has
demonstrated
neuroprotective
effects
a
TAU-dependent
FTD
mouse
model,
reducing
This
suggests
DMF
repositioning
potential
for
treatment.
Until
now,
trial
had
been
conducted
analyze
effect
of
on
TDP-43-dependent
FTD.
In
this
study,
we
aimed
determine
efficacy
TDP-43-related
model
that
exhibits
early
cognitive
impairment.
Mice
received
oral
every
other
day
from
presymptomatic
symptomatic
stages.
By
post-natal
(PND)
60,
improvement
function
already
evident,
becoming
even
more
pronounced
by
PND90.
enhancement
correlates
neuroprotection
observed
dentate
gyrus
reduction
astrogliosis
stratum
lacunosum-moleculare
zone.
At
prefrontal
cortex
(PFC)
level,
also
observed,
accompanied
astrogliosis.
Collectively,
our
results
suggest
application
patients
Cerebral Cortex,
Journal Year:
2025,
Volume and Issue:
35(4)
Published: April 1, 2025
Abstract
White
matter,
comprising
approximately
50%
of
the
human
brain,
is
crucial
for
efficient
neuronal
signaling
and
a
wide
range
brain
functions,
including
social
cognition,
sensation,
memory,
motor
control,
information
integration
across
cortical
regions
in
service
perception
cognition.
composed
myelinated
axons,
results
from
complex
interactions
between
different
cell
types,
with
oligodendrocytes
(OLs)
microglia
playing
integral
roles.
Microglia,
brain's
resident
immune
cells,
regulate
oligodendrogenesis
through
phagocytosis
molecular
signaling,
example
cytokines,
which
promote
inhibit
maturation
stages
OL
lineage
cells.
Maternal
activation
(MIA)
recognized
risk
factor
neurodevelopmental
disorders,
especially
autism
spectrum
disorder
(ASD).
The
physiological
presentation
ASD
includes
white
matter
abnormalities
dysregulation.
Emerging
evidence
indicates
that
MIA
may
reduce
microglial
reactivity
alter
cytokine
release
offspring,
potentially
disrupting
delicate
balance
required
proper
development.
Understanding
intricate
interplay
oligodendrocytes,
microglia,
inflammation,
development
context
provides
valuable
insights
into
etiology
core
symptoms
possible
therapeutic
targets.
The Neuroscientist,
Journal Year:
2024,
Volume and Issue:
unknown
Published: May 20, 2024
Microglia
are
a
specialized
type
of
neuroimmune
cells
that
undergo
morphological
and
molecular
changes
through
multiple
signaling
pathways
in
response
to
pathological
protein
aggregates,
neuronal
death,
tissue
injury,
or
infections.
express
Trem2,
which
serves
as
receptor
for
multitude
ligands
enhancing
their
phagocytic
activity.
Trem2
has
emerged
critical
modulator
microglial
activity,
especially
many
neurodegenerative
disorders.
Human
TREM2
mutations
associated
with
an
increased
risk
developing
Alzheimer
disease
(AD)
other
diseases.
plays
dual
roles
neuroinflammation
more
specifically
disease-associated
microglia.
Most
recent
developments
on
the
mechanisms
emphasizing
its
role
uptake
clearance
amyloid
β
(Aβ)
aggregates
debris
help
protect
preserve
brain,
encouraging.
Although
normally
stimulates
defense
mechanisms,
dysregulation
can
intensify
inflammation,
poses
major
therapeutic
challenges.
Recent
approaches
targeting
via
agonistic
antibodies
gene
therapy
methodologies
present
possible
avenues
reducing
burden
This
review
highlights
promise
target,
Aβ-associated
AD,
calls
mechanistic
investigations
understand
context-specific
effective
therapies
against
Journal of Alzheimer s Disease,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 2, 2025
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
characterized
by
the
accumulation
of
amyloid-β
plaques,
neurofibrillary
tangles,
and
chronic
neuroinflammation.
Microglial
cells,
resident
immune
cells
in
central
nervous
system,
play
crucial
role
pathogenesis
AD.
Microglia
can
undergo
polarization,
shifting
between
pro-inflammatory
(M1)
anti-inflammatory
(M2)
phenotypes
response
to
different
stimuli.
Dysregulation
microglial
polarization
towards
phenotype
leads
release
inflammatory
cytokines,
oxidative
stress,
synaptic
dysfunction.
These
processes
contribute
neuronal
damage
cognitive
decline
However,
several
challenges
remain
this
field.
The
complex
molecular
mechanisms
governing
AD
need
be
further
elucidated.
In
review,
we
discuss
underlying
its
implications
progression.
Brain and Behavior,
Journal Year:
2024,
Volume and Issue:
14(5)
Published: May 1, 2024
Abstract
Introduction
Chronic
adolescent
stress
profoundly
affects
prefrontal
cortical
networks
regulating
top‐down
behavior
control.
However,
the
neurobiological
pathways
contributing
to
stress‐induced
alterations
in
brain
and
remain
largely
unknown.
influences
growth
factors
immune
responses,
which
may,
turn,
disrupt
maturation
function
of
networks.
The
tumor
necrosis
factor
alpha‐converting
enzyme/a
disintegrin
metalloproteinase
17
(TACE/ADAM17)
is
a
sheddase
with
essential
functions
maturation,
behavior,
inflammatory
responses.
This
study
aimed
determine
impact
on
cortex
whether
TACE/ADAM17
plays
role
these
Methods
We
used
Lewis
rat
model
that
incorporates
critical
elements
chronic
psychosocial
stress,
such
as
uncontrollability,
unpredictability,
lack
social
support,
re‐experiencing
trauma.
Results
during
adolescence
reduced
acoustic
startle
reflex
interactions
while
increasing
extracellular
free
water
content
mRNA
levels
medial
cortex.
altered
various
ethological
behavioral
domains
observation
home
cages
(decreased
ingestive
behaviors
increased
walking,
grooming,
rearing
behaviors).
A
group
rats
was
injected
intracerebrally
either
novel
Accell™
SMARTpool
siRNA
or
corresponding
vehicle
(control).
RNAscope
Multiplex
Fluorescent
v2
Assay
visualize
expression.
Automated
puncta
quantification
analyses
demonstrated
administration
(59%
reduction
relative
control).
found
received
exhibited
eating
patterns
(e.g.,
food
intake
time
feeding
zone
light
cycle).
Conclusion
supports
sensitive
suggests
may
be
involved
responses
stress.
Glia,
Journal Year:
2024,
Volume and Issue:
72(9), P. 1544 - 1554
Published: June 5, 2024
Abstract
The
nervous
and
the
immune
systems
undergo
a
continuous
cross
talk,
starting
from
early
development
continuing
throughout
adulthood
aging.
Defects
in
this
talk
contribute
to
neurodevelopmental
neurodegenerative
diseases.
Microglia
are
resident
cells
brain
that
primarily
involved
bidirectional
communication.
Among
microglial
genes,
trem2
is
key
player,
controlling
functional
state
of
microglia
being
at
forefront
many
processes
require
interaction
between
other
components,
such
as
neurons
oligodendrocytes.
present
review
focuses
on
developmental
window,
describing
which
TREM2
involved,
including
modulation
synapse
formation
elimination,
control
neuronal
bioenergetic
states
well
contribution
myelination
circuit
formation.
By
causing
imbalances
during
these
maturation
phases,
dysfunctional
may
have
striking
impact
adult
brain,
making
it
more
sensitive
target
for
insults
occurring
