Journal of Clinical Investigation,
Journal Year:
2020,
Volume and Issue:
131(1)
Published: Sept. 29, 2020
Dysfunction
of
immune
and
vascular
systems
has
been
implicated
in
aging
Alzheimer
disease;
however,
their
interrelatedness
remains
poorly
understood.
The
complement
pathway
is
a
well-established
regulator
innate
immunity
the
brain.
Here,
we
report
robust
age-dependent
increases
inflammation,
peripheral
lymphocyte
infiltration,
blood-brain
barrier
(BBB)
permeability.
These
phenotypes
were
subdued
by
global
inactivation
endothelial
cell–specific
ablation
C3ar1.
Using
an
vitro
model
BBB,
identified
intracellular
Ca2+
as
downstream
effector
C3a/C3aR
signaling
functional
mediator
cadherin
junction
integrity.
Endothelial
C3ar1
also
dampened
microglia
reactivity
improved
hippocampal
cortical
volumes
brain,
demonstrating
crosstalk
between
brain
vasculature
dysfunction
cell
activation
neurodegeneration.
Further,
prominent
C3aR-dependent
inflammation
was
observed
tau-transgenic
mouse
model.
Our
studies
suggest
that
heightened
through
cells
promotes
BBB
contributes
to
overall
neuroinflammation
neurodegenerative
disease.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: July 12, 2023
Abstract
Studies
in
neurodegenerative
diseases,
including
Alzheimer’s
disease,
Parkinson’s
disease
and
Amyotrophic
lateral
sclerosis,
Huntington’s
so
on,
have
suggested
that
inflammation
is
not
only
a
result
of
neurodegeneration
but
also
crucial
player
this
process.
Protein
aggregates
which
are
very
common
pathological
phenomenon
can
induce
neuroinflammation
further
aggravates
protein
aggregation
neurodegeneration.
Actually,
even
happens
earlier
than
aggregation.
Neuroinflammation
induced
by
genetic
variations
CNS
cells
or
peripheral
immune
may
deposition
some
susceptible
population.
Numerous
signaling
pathways
range
been
to
be
involved
the
pathogenesis
neurodegeneration,
although
they
still
far
from
being
completely
understood.
Due
limited
success
traditional
treatment
methods,
blocking
enhancing
inflammatory
considered
promising
strategies
for
therapy
many
them
got
exciting
results
animal
models
clinical
trials.
Some
them,
few,
approved
FDA
usage.
Here
we
comprehensively
review
factors
affecting
major
pathogenicity
sclerosis.
We
summarize
current
strategies,
both
clinic,
diseases.
Cellular and Molecular Immunology,
Journal Year:
2021,
Volume and Issue:
18(11), P. 2489 - 2501
Published: Sept. 30, 2021
Abstract
The
vascular
blood–brain
barrier
is
a
highly
regulated
interface
between
the
blood
and
brain.
Its
primary
function
to
protect
central
neurons
while
signaling
presence
of
systemic
inflammation
infection
brain
enable
protective
sickness
behavior
response.
With
increasing
degrees
duration
inflammation,
becomes
more
permeable
solutes,
undergoes
an
increase
in
lymphocyte
trafficking,
infiltrated
by
innate
immune
cells;
endothelial
cell
damage
may
occasionally
occur.
Perturbation
neuronal
results
clinical
features
encephalopathy.
Here,
molecular
cellular
anatomy
reviewed,
first
healthy
context
second
inflammatory
context.
Distinct
from
mediators
barrier’s
response
several
moderators
influence
direction
magnitude
at
genetic,
system,
levels.
These
include
sex,
genetic
background,
age,
pre-existing
pathology,
comorbidity,
gut
dysbiosis.
Further
progress
required
define
measure
order
explain
heterogeneity
observed
animal
human
studies.
Molecular Psychiatry,
Journal Year:
2022,
Volume and Issue:
27(6), P. 2659 - 2673
Published: March 31, 2022
Abstract
The
blood-brain
barrier
(BBB)
is
vital
for
maintaining
brain
homeostasis
by
enabling
an
exquisite
control
of
exchange
compounds
between
the
blood
and
parenchyma.
Moreover,
BBB
prevents
unwanted
toxins
pathogens
from
entering
brain.
This
barrier,
however,
breaks
down
with
age
further
disruption
a
hallmark
many
age-related
disorders.
Several
drugs
have
been
explored,
thus
far,
to
protect
or
restore
function.
With
recent
connection
gut
microbiota,
microbial-derived
metabolites
explored
their
capabilities
physiology.
review,
will
focus
on
components
that
make
up
BBB,
dissect
levels
discuss
current
therapeutics
maintain
integrity
discoveries
effects
Molecular Neurodegeneration,
Journal Year:
2022,
Volume and Issue:
17(1)
Published: Nov. 8, 2022
Alzheimer's
disease
(AD)
is
the
most
common
cause
of
dementia
worldwide,
and
its
prevalence
rapidly
increasing
due
to
extended
lifespans.
Among
number
genetic
risk
factors
identified,
apolipoprotein
E
(APOE)
gene
remains
strongest
prevalent,
impacting
more
than
half
all
AD
cases.
While
ε4
allele
APOE
significantly
increases
risk,
ε2
protective
relative
ε3
allele.
These
alleles
encode
three
apoE
protein
isoforms
that
differ
at
two
amino
acid
positions.
The
primary
physiological
function
mediate
lipid
transport
in
brain
periphery;
however,
additional
functions
diverse
biological
have
been
recognized.
Pathogenically,
seeds
amyloid-β
(Aβ)
plaques
with
apoE4
driving
earlier
abundant
amyloids.
ApoE
also
differential
effects
on
multiple
Aβ-related
or
Aβ-independent
pathways.
complexity
biology
pathobiology
presents
challenges
designing
effective
apoE-targeted
therapeutic
strategies.
This
review
examines
key
pathobiological
pathways
related
targeting
strategies
a
specific
focus
latest
technological
advances
tools.
