The Importance of Phosphoinositide 3-Kinase in Neuroinflammation
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(21), P. 11638 - 11638
Published: Oct. 30, 2024
Neuroinflammation,
characterised
by
the
activation
of
immune
cells
in
central
nervous
system
(CNS),
plays
a
dual
role
both
protecting
against
and
contributing
to
progression
neurodegenerative
diseases,
such
as
Alzheimer's
disease
(AD)
multiple
sclerosis
(MS).
This
review
explores
phosphoinositide
3-kinase
(PI3K),
key
enzyme
involved
cellular
survival,
proliferation,
inflammatory
responses,
within
context
neuroinflammation.
Two
PI3K
isoforms
interest,
PI3Kγ
PI3Kδ,
are
specific
regulation
CNS
cells,
microglia,
astrocytes,
neurons,
oligodendrocytes,
influencing
pathways,
Akt,
mTOR,
NF-κB,
that
control
cytokine
production,
cell
activation,
neuroprotection.
The
dysregulation
signalling
is
implicated
chronic
neuroinflammation,
exacerbation
diseases.
Preclinical
studies
show
promise
targeting
neuronal
disorders
using
inhibitors,
AS605240
(PI3Kγ)
idelalisib
(PI3Kδ),
which
have
reduced
inflammation,
microglial
death
vivo
models
AD.
However,
clinical
translation
these
inhibitors
faces
challenges,
including
blood-brain
barrier
(BBB)
permeability,
isoform
specificity,
long-term
safety
concerns.
highlights
therapeutic
potential
modulation
neuroinflammatory
identifying
gaps
current
research,
particularly
need
for
brain-penetrating
isoform-specific
inhibitors.
These
findings
underscore
importance
future
research
develop
targeted
therapies
can
effectively
modulate
activity
provide
neuroprotection
disorders.
Language: Английский
The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation
Neurology International,
Journal Year:
2025,
Volume and Issue:
17(1), P. 6 - 6
Published: Jan. 13, 2025
Neuroinflammation
is
a
blanket
term
that
describes
the
body’s
complex
inflammatory
response
in
central
nervous
system
(CNS).
It
encompasses
phenotype
shift
to
proinflammatory
state,
release
of
cytokines,
recruitment
peripheral
immune
cells,
and
wide
variety
other
processes.
has
been
implicated
nearly
every
major
CNS
disease
ranging
from
Alzheimer’s
brain
cancer.
Understanding
modeling
neuroinflammation
critical
for
identification
novel
therapeutic
targets
treatment
diseases.
Unfortunately,
translation
findings
non-human
models
left
much
be
desired.
This
review
systematically
discusses
role
human
pluripotent
stem
cell
(hPSC)-derived
glia
supporting
cells
within
CNS,
including
astrocytes,
microglia,
oligodendrocyte
precursor
pericytes,
endothelial
describe
state
field
hope
future
discoveries.
hPSC-derived
offer
an
expanded
potential
study
pathobiology
immunomodulatory
cascades
impact
progression.
While
progress
made
development
models,
there
explore
application
these
understand
CNS.
Language: Английский
A dual role for pleiotrophin in modulating inflammation and myelination in the presence of chondroitin sulfate proteoglycans after nervous system injury
Frontiers in Cellular Neuroscience,
Journal Year:
2025,
Volume and Issue:
19
Published: Feb. 27, 2025
Chondroitin
sulfate
proteoglycans
(CSPGs),
key
components
of
the
extracellular
matrix
and
glial
scar
that
forms
around
central
nervous
system
(CNS)
injuries,
are
recognized
for
hindering
neuronal
regeneration.
We
previously
demonstrated
potential
pleiotrophin
(PTN)
to
induce
neurite
outgrowth
even
in
presence
inhibitory
CSPGs.
The
effects
PTN
on
microglia
oligodendrocytes
not
well
described.
Here,
we
examined
how
administration
alters
differentiation
oligodendrocyte
precursor
cells
(OPCs)
into
mature
CSPGs
using
vitro
cell
culture
model.
Moreover,
explored
inflammatory
activity
with
without
stimulation
(IFN-γ)
a
CSPG-rich
environment.
data
showed
CSPG
inhibited
OPCs
oligodendrocytes.
induced
dose-dependent
oligodendrocytes,
an
optimal
effect
at
10
nM
PTN.
modified
immunological
response
CSPGs,
reduced
proinflammatory
was
further
by
administration,
contrast
increased
release
metalloproteinases
(MMP
9).
However,
when
IFN-γ-activated
were
treated
PTN,
signaling
stimulated
higher
concentrations
(10
100
nM).
Overall,
our
results
indicate
can
overcome
modulate
inflammation
mediated
from
microglia.
Collectively,
these
findings
demonstrate
effectively
counteract
while
also
modulating
microglial
responses
reduce
increase
MMP-9
release.
Thus,
has
great
improve
remyelination
neuroprotective
strategies
treatment
demyelinating
diseases
or
any
injury.
Language: Английский
Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)
Brain Sciences,
Journal Year:
2024,
Volume and Issue:
14(11), P. 1101 - 1101
Published: Oct. 30, 2024
Obesity,
type
2
diabetes
(T2D),
and
Alzheimer's
disease
(AD)
are
pathologies
that
affect
millions
of
people
worldwide.
They
have
no
effective
therapy
difficult
to
prevent
control
when
they
develop.
It
has
been
known
for
many
years
these
diseases
pathogenic
aspects
in
common.
We
highlight
this
review
neuroglial
cells
(astroglia,
oligodendroglia,
microglia)
play
a
vital
role
the
origin,
clinical-pathological
development,
course
brain
neurodegeneration.
Moreover,
we
include
new
results
T2D-AD
mouse
model
(APP+PS1
mice
on
high-calorie
diet)
investigating.
Language: Английский
The Role of Inflammatory Cascade and Reactive Astrogliosis in Glial Scar Formation Post-spinal Cord Injury
Cellular and Molecular Neurobiology,
Journal Year:
2024,
Volume and Issue:
44(1)
Published: Nov. 23, 2024
Reactive
astrogliosis
and
inflammation
are
pathologic
hallmarks
of
spinal
cord
injury.
After
injury,
dysfunction
glial
cells
(astrocytes)
results
in
scar
formation,
which
limits
neuronal
regeneration.
The
blood–spinal
barrier
maintains
the
structural
functional
integrity
does
not
allow
blood
vessel
components
to
leak
into
microenvironment.
disruption
causes
an
imbalance
immunological
This
triggers
process
neuroinflammation,
facilitated
by
actions
microglia,
neutrophils,
cells,
cytokines
production.
Recent
work
has
revealed
two
phenotypes
astrocytes,
A1
A2,
where
A2
a
protective
type,
releases
neurotoxins,
further
promoting
formation.
Here,
we
first
describe
current
understanding
microenvironment,
both
pre-,
post-injury,
role
different
context
forms
essential
update
on
cellular
molecular
events
following
We
aim
explore
in-depth
signaling
pathways
mediators
that
trigger
astrocyte
activation
review
will
discuss
activated
astrocytes
other
their
collaborative
development
gliosis
through
inflammatory
responses.
Language: Английский