Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis.
[gm1 gangliosidosis]
Lysosomal
β-galactosidase
(
β-
Gal
)
deficiency
causes
a
group
of
disorders
that
include
neuronopathic
GM
1
gangliosidosis
and
non-neuronopathic
Morquio
B
disease
.
We
have
previously
proposed
the
use
of
small
molecule
ligands
of
β-
Gal
as
pharmacological
chaperones
(
PCs
)
for
the
treatment
of
GM
1
gangliosidosis
brain
pathology
.
Although
it
is
still
under
development
,
PC
therapy
has
yielded
promising
preclinical
results
in
several
lysosomal
diseases
.
In
this
study
,
we
evaluated
the
effect
of
bicyclic
1
-
deoxygalactonojirimycin
(
DGJ
)
derivative
of
the
sp
(
2
)
-
iminosugar
type
,
namely
5
N
,
6
S-
(
N
'
-
butyliminomethylidene
)
-
6
-
thio-
1
-
deoxygalactonojirimycin
(
6
S-NBI-DGJ
)
,
as
a
novel
PC
for
human
mutant
β-
Gal
.
In
vitro
,
6
S-NBI-DGJ
had
the
ability
to
inhibit
the
activity
of
human
β-
Gal
in
a
competitive
manner
and
was
able
to
protect
this
enzyme
from
heat-induced
degradation
.
Computational
analysis
supported
that
the
rigid
glycone
bicyclic
core
of
6
S-NBI-DGJ
binds
to
the
active
site
of
the
enzyme
,
with
the
aglycone
N
'
-
butyl
substituent
,
in
a
precise
E
-
orientation
,
located
at
a
hydrophobic
region
nearby
.
Chaperone
potential
profiling
indicated
significant
increases
of
enzyme
activity
in
24
of
88
β-
Gal
mutants
,
including
four
common
mutations
.
Finally
,
oral
administration
of
6
S-NBI-DGJ
ameliorated
the
brain
pathology
of
GM
1
gangliosidosis
model
mice
.
These
results
suggest
that
6
S-NBI-DGJ
is
a
novel
PC
that
may
be
effective
on
a
broad
range
of
β-
Gal
mutants
.
Diseases
Validation
Diseases presenting
"broad range"
symptom
acute rheumatic fever
congenital toxoplasmosis
cowden syndrome
cystinuria
dystrophic epidermolysis bullosa
gm1 gangliosidosis
hereditary cerebral hemorrhage with amyloidosis
kallmann syndrome
neuralgic amyotrophy
severe combined immunodeficiency
typhoid
waldenström macroglobulinemia
well-differentiated liposarcoma
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom