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The role of microglia in human disease: therapeutic tool or target?
[x-linked adrenoleukodystrophy]
Microglia
have
long
been
the
focus
of
much
attention
due
to
their
strong
proliferative
response
(
microgliosis
)
to
essentially
any
kind
of
damage
to
the
CNS
.
More
recently
,
we
reached
the
realization
that
these
cells
play
specific
roles
in
determining
progression
and
outcomes
of
essentially
all
CNS
disease
.
Thus
,
microglia
has
ceased
to
be
viewed
as
an
accessory
to
underlying
pathologies
and
has
now
taken
center
stage
as
a
therapeutic
target
.
Here
,
we
review
how
our
understanding
of
microglia
's
involvement
in
promoting
or
limiting
the
pathogenesis
of
diseases
such
as
amyotrophic
lateral
sclerosis
,
Alzheimer
's
disease
,
Huntington
's
disease
,
multiple
sclerosis
,
X-
linked
adrenoleukodystrophy
(
X-
ALD
)
and
lysosomal
storage
diseases
(
LSD
)
has
changed
over
time
.
While
strategies
to
suppress
the
deleterious
and
promote
the
virtuous
functions
of
microglia
will
undoubtedly
be
forthcoming
,
replacement
of
these
cells
has
already
proven
its
usefulness
in
a
clinical
setting
.
Over
the
past
few
years
,
we
have
reached
the
realization
that
microglia
have
a
developmental
origin
that
is
distinct
from
that
of
bone
marrow-derived
myelomonocytic
cells
.
Nevertheless
,
microglia
can
be
replaced
,
in
specific
situations
,
by
the
progeny
of
hematopoietic
stem
cells
(
HSCs
)
,
pointing
to
a
strategy
to
engineer
the
CNS
environment
through
the
transplantation
of
modified
HSCs
.
Thus
,
microglia
replacement
has
been
successfully
exploited
to
deliver
therapeutics
to
the
CNS
in
human
diseases
such
as
X-
ALD
and
LSD
.
With
this
outlook
in
mind
,
we
will
discuss
the
evidence
existing
so
far
for
microglial
involvement
in
the
pathogenesis
and
the
therapy
of
specific
CNS
disease
.
Diseases
Validation
Diseases presenting
"by the progeny of hematopoietic stem cells"
symptom
x-linked adrenoleukodystrophy
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