Molecular Neurodegeneration,
Год журнала:
2017,
Номер
12(1)
Опубликована: Май 26, 2017
Alzheimer's
disease
(AD)
is
a
highly
heritable
complex
with
no
current
effective
prevention
or
treatment.
The
majority
of
drugs
developed
for
AD
focus
on
the
amyloid
cascade
hypothesis,
which
implicates
Aß
plaques
as
causal
factor
in
disease.
However,
it
possible
that
other
underexplored
disease-associated
pathways
may
be
more
fruitful
targets
drug
development.
Findings
from
gene
network
analyses
implicate
immune
networks
being
enriched
AD;
many
genes
these
fall
within
genomic
regions
contain
common
and
rare
variants
are
associated
increased
risk
developing
AD.
Of
genes,
several
(including
CR1,
SPI1,
MS4As,
TREM2,
ABCA7,
CD33,
INPP5D)
expressed
by
microglia,
resident
cells
brain.
We
summarize
genetics
findings
microglial
involved
AD,
well
studies
have
looked
at
expression
function
microglia
context
propose
contributing
to
non-Aß-dependent
fashion.
Annual Review of Immunology,
Год журнала:
2017,
Номер
35(1), С. 441 - 468
Опубликована: Фев. 22, 2017
Microglia
are
resident
cells
of
the
brain
that
regulate
development,
maintenance
neuronal
networks,
and
injury
repair.
serve
as
macrophages
but
distinct
from
other
tissue
owing
to
their
unique
homeostatic
phenotype
tight
regulation
by
central
nervous
system
(CNS)
microenvironment.
They
responsible
for
elimination
microbes,
dead
cells,
redundant
synapses,
protein
aggregates,
particulate
soluble
antigens
may
endanger
CNS.
Furthermore,
primary
source
proinflammatory
cytokines,
microglia
pivotal
mediators
neuroinflammation
can
induce
or
modulate
a
broad
spectrum
cellular
responses.
Alterations
in
functionality
implicated
development
aging,
well
neurodegeneration.
Recent
observations
about
ontogeny
combined
with
extensive
gene
expression
profiling
novel
tools
study
biology
have
allowed
us
characterize
microglial
phenotypes
during
homeostasis,
disease.
In
this
article,
we
review
recent
advances
our
understanding
microglia,
contribution
involvement
Moreover,
highlight
complexity
targeting
therapeutic
intervention
neurodegenerative
diseases.
Alzheimer s & Dementia Translational Research & Clinical Interventions,
Год журнала:
2018,
Номер
4(1), С. 575 - 590
Опубликована: Янв. 1, 2018
Abstract
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
that
characterized
by
cognitive
decline
and
the
presence
of
two
core
pathologies,
amyloid
β
plaques
neurofibrillary
tangles.
Over
last
decade,
sustained
immune
response
in
brain
has
emerged
as
third
pathology
AD.
The
activation
brain's
resident
macrophages
(microglia)
other
cells
been
demonstrated
to
exacerbate
both
tau
may
serve
link
pathogenesis
disorder.
In
following
review,
we
provide
an
overview
inflammation
AD
detailed
coverage
number
microglia‐related
signaling
mechanisms
have
implicated
Additional
information
on
microglia
cytokines
are
also
reviewed.
We
review
potential
connection
risk
factors
for
how
they
be
related
inflammatory
mechanisms.
The Journal of Cell Biology,
Год журнала:
2017,
Номер
217(2), С. 459 - 472
Опубликована: Дек. 1, 2017
Proliferation
and
activation
of
microglia
in
the
brain,
concentrated
around
amyloid
plaques,
is
a
prominent
feature
Alzheimer’s
disease
(AD).
Human
genetics
data
point
to
key
role
for
pathogenesis
AD.
The
majority
risk
genes
AD
are
highly
expressed
(and
many
selectively
expressed)
by
brain.
There
mounting
evidence
that
protect
against
incidence
AD,
as
impaired
microglial
activities
altered
responses
β-amyloid
associated
with
increased
risk.
On
other
hand,
there
also
abundant
activated
can
be
harmful
neurons.
Microglia
mediate
synapse
loss
engulfment
synapses,
likely
via
complement-dependent
mechanism;
they
exacerbate
tau
pathology
secrete
inflammatory
factors
injure
neurons
directly
or
neurotoxic
astrocytes.
Gene
expression
profiles
indicate
multiple
states
neurodegenerative
settings,
which
might
explain
disparate
roles
development
progression
pathology.
