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Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases.
[x-linked adrenoleukodystrophy]
It
is
well
established
that
glial
cells
have
critical
roles
in
the
inflammatory
processes
in
the
central
nervous
system
(
CNS
)
.
These
cells
can
be
activated
by
a
variety
of
endogenous
and
exogenous
stimuli
(
i
.
e
.
gliosis
)
and
can
produce
high
levels
of
bioactive
compounds
that
are
noxious
for
neuronal
cell
function
.
One
of
the
most
important
molecules
released
by
activated
glial
cells
is
the
bioactive
free
radical
nitric
oxide
(
NO
)
.
Although
NO
physiologically
acts
as
both
neuromodulator
and
neurotransmitter
in
the
brain
,
excess
production
of
NO
by
glial
cells
has
diverse
harmful
effects
on
neuronal
function
,
causing
neuronal
cell
injury
/
death
.
The
production
of
NO
is
induced
by
overexpression
of
the
inducible
isoform
of
NO
synthase
(
iNOS
)
enzyme
in
glial
cells
.
In
this
review
,
we
describe
the
possible
mechanisms
that
underlie
the
iNOS-mediated
overproduction
of
glial
NO
in
several
pediatric
and
adult
neuropathologic
conditions
such
as
periventricular
leukomalacia
(
PVL
)
,
Krabbe
's
disease
,
X-
linked
adrenoleukodystrophy
(
ALD
)
and
multiple
sclerosis
(
MS
)
.
We
specifically
discuss
various
signaling
cascades
that
activate
several
transcription
factors
involved
in
the
iNOS
expression
in
both
astrocytes
and
microglia
.
We
also
discuss
the
consequences
of
iNOS-mediated
NO
production
in
neuroinflammatory
diseases
including
MS
.
A
complete
understanding
of
the
regulation
of
iNOS
expression
in
glial
cells
and
the
mechanisms
by
which
iNOS-mediated
NO
production
is
involved
in
neuroinflammation
can
provide
new
insights
into
the
identification
of
novel
targets
for
therapeutic
intervention
in
NO-mediated
neurologic
diseases
.
Diseases
Validation
Diseases presenting
"central nervous system"
symptom
22q11.2 deletion syndrome
adrenomyeloneuropathy
alexander disease
aniridia
aromatase deficiency
canavan disease
child syndrome
classical phenylketonuria
congenital toxoplasmosis
cowden syndrome
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
fabry disease
gm1 gangliosidosis
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
kabuki syndrome
kallmann syndrome
kindler syndrome
krabbe disease
lamellar ichthyosis
legionellosis
liposarcoma
malignant atrophic papulosis
monosomy 21
neonatal adrenoleukodystrophy
phenylketonuria
proteus syndrome
scrub typhus
severe combined immunodeficiency
sneddon syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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