Mucopolysaccharidosis Type IIIE: A Real Human Disease or a Diagnostic Pitfall?
Diagnostics,
Год журнала:
2024,
Номер
14(16), С. 1734 - 1734
Опубликована: Авг. 9, 2024
Mucopolysaccharidoses
(MPS)
comprise
a
group
of
12
metabolic
disorders
where
defects
in
specific
enzyme
activities
lead
to
the
accumulation
glycosaminoglycans
(GAGs)
within
lysosomes.
This
classification
expands
13
when
considering
MPS
IIIE.
type
MPS,
associated
with
pathogenic
variants
Язык: Английский
Perspective Chapter: Next-Generation Sequencing and Variant Cataloging for Screening and Diagnosis of Sphingolipidoses and Mucopolysaccharidoses
IntechOpen eBooks,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
This
chapter
provides
a
comprehensive
examination
of
how
next-generation
sequencing
(NGS)
technologies
are
transforming
prenatal
and
neonatal
care,
particularly
in
the
diagnosis
lysosomal
diseases
(LDs).
These
rare,
inherited
conditions
caused
by
defects
metabolism.
If
not
detected
treated
early,
they
can
lead
to
significant
disabilities
reduced
life
expectancy.
The
specifically
focuses
on
use
NGS
diagnose
screen
sphingolipidoses
(SLDs)
mucopolysaccharidoses
(MPSs).
It
covers
molecular
pathogenesis,
classification,
main
symptomatology
diseases.
reviews
progress
made
identifying
genes
associated
with
SLDs
MPSs
cataloging
clinically
relevant
genetic
variants.
Additionally,
it
highlights
growing
adoption
for
screening
institutions
such
as
academic
research
centers,
private
healthcare
providers,
government
health
agencies.
also
discusses
challenges
implementation,
regulation,
outlines
future
directions
its
application
medicine.
Язык: Английский
An Overview of Property, Design, and Functionality of Linkers for Fusion Protein Construction
Proteins Structure Function and Bioinformatics,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 18, 2025
ABSTRACT
Linkers
are
naturally
occurring
short
amino
acid
sequences
that
used
to
separate
domains
within
a
protein.
The
advent
of
recombinant
DNA
technology
has
made
it
possible
combine
two
interacting
partners
by
introducing
artificial
linkers
often,
allow
for
the
production
stable
and
functional
proteins.
Glycine‐rich
useful
transient
interactions,
especially
where
interaction
is
weak,
covalently
linking
proteins
forming
protein–protein
complex.
These
have
also
been
generate
dimers
connect
independent
create
ligand
binding
site
or
recognition
sequence.
Various
structures
linked
protein
complexes
described
using
nuclear
magnetic
resonance
methods,
cryo‐electron
microscopy
techniques,
X‐ray
crystallography;
in
addition,
several
complexes,
improve
solubility,
obtain
investigated,
design
engineering
linker
fusion
discussed.
Therefore,
one
main
factors
optimization
their
flexibility,
which
can
directly
contribute
physical
distance
between
describe
tendency
maintain
conformation
during
expression.
We
summarize
research
on
bioinformatics
be
predict
spatial
structure
To
perform
simulations
drug
molecule
design,
future
will
concentrate
various
correlation
models.
Язык: Английский
Potential Targeting Mechanisms for Bone-Directed Therapies
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(15), С. 8339 - 8339
Опубликована: Июль 30, 2024
Bone
development
is
characterized
by
complex
regulation
mechanisms,
including
signal
transduction
and
transcription
factor-related
pathways,
glycobiological
processes,
cellular
interactions,
transportation
and,
importantly,
chemical
formation
resulting
from
hydroxyapatite.
Any
abnormal
in
the
bone
processes
causes
skeletal
system-related
problems.
To
some
extent,
avascularity
of
cartilage
makes
drug
delivery
more
challenging
than
that
soft
tissues.
Recent
studies
have
implemented
many
novel
bone-targeting
approaches
to
overcome
drawbacks.
However,
none
these
strategies
fully
corrects
dysfunction,
particularly
growth
plate-related
ones.
Although
direct
recombinant
enzymes
(e.g.,
Vimizim
for
Morquio,
Cerezyme
Gaucher,
Elaprase
Hunter,
Mepsevii
Sly
diseases)
or
hormone
infusions
(estrogen
osteoporosis
osteoarthritis),
traditional
gene
infusion
viral
non-viral
vectors
with
no
modifications
on
capsid,
envelope,
nanoparticles),
cell
therapy
(healthy
marrow
hematopoietic
stem
transplantation)
partially
improve
lesions,
methods
must
be
addressed
regarding
target
specificity,
less
immunogenicity,
duration
circulation.
In
addition
improvements
delivery,
potential
mechanisms
involving
receptor-regulated
pathways
has
also
been
utilized.
Targeted
using
organic
inorganic
compounds
a
promising
approach
mostly
preclinical
settings
future
clinical
translation.
This
review
comprehensively
summarizes
current
based
structure
remodeling
concepts
while
emphasizing
systems.
Язык: Английский
Targeting Neurological Aspects of Mucopolysaccharidosis Type II: Enzyme Replacement Therapy and Beyond
BioDrugs,
Год журнала:
2024,
Номер
38(5), С. 639 - 655
Опубликована: Авг. 23, 2024
Mucopolysaccharidosis
type
II
(MPS
II)
is
a
rare,
pediatric,
neurometabolic
disorder
due
to
the
lack
of
activity
lysosomal
hydrolase
iduronate
2-sulfatase
(IDS),
normally
degrading
heparan
sulfate
and
dermatan
within
cell
lysosomes.
The
deficit
caused
by
mutations
affecting
IDS
gene,
leading
pathological
accumulation
both
glycosaminoglycans
in
compartment
extracellular
matrix
most
body
districts.
Although
continuum
clinical
phenotypes
described,
two
main
forms
are
commonly
recognized-attenuated
severe-the
latter
being
characterized
an
earlier
faster
progression
progressive
impairment
central
nervous
system
(CNS)
functions.
However,
attenuated
have
also
been
recently
described
as
presenting
some
neurological
involvement,
although
less
deep,
such
deficits
attention
hearing
loss.
treatment
for
disease
represented
enzyme
replacement
therapy
(ERT),
applied
several
countries
since
2006,
which,
albeit
showing
partial
efficacy
on
peripheral
organs,
exhibited
very
poor
bones
heart,
total
inefficacy
CNS
impairment,
inability
recombinant
cross
blood-brain
barrier
(BBB).
Together
with
ERT,
whose
design
enhancements,
performed
last
few
years,
allowed
possible
brain
penetration
drug
through
BBB,
other
therapeutic
approaches
aimed
at
targeting
involvement
MPS
were
proposed
evaluated
decades,
intrathecal
intracerebroventricular
ex
vivo
gene
therapy,
or
adeno-associated
viral
vector
(AAV)
therapy.
aim
this
review
summarize
aspects
addition
current
options,
particular
emphasis
ones
CNS-targeted
explored
years.
Язык: Английский
Mucopolysaccharidosis-Plus Syndrome: Is This a Type of Mucopolysaccharidosis or a Separate Kind of Metabolic Disease?
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9570 - 9570
Опубликована: Сен. 4, 2024
Several
years
ago,
dozens
of
cases
were
described
in
patients
with
symptoms
very
similar
to
mucopolysaccharidosis
(MPS).
This
new
disease
entity
was
as
mucopolysaccharidosis-plus
syndrome
(MPSPS).
The
name
the
indicates
that
addition
typical
conventional
MPS,
develop
other
features
such
congenital
heart
defects
and
kidney
hematopoietic
system
disorders.
are
highly
advanced,
usually
do
not
survive
past
second
year
life.
MPSPS
is
inherited
an
autosomal
recessive
manner
caused
by
a
homozygous-specific
mutation
gene
encoding
VPS33A
protein.
To
date,
it
has
been
41
patients.
Patients
exhibited
excessive
excretion
glycosaminoglycans
(GAGs)
urine
exceptionally
high
levels
heparan
sulfate
plasma,
but
accumulation
substrates
decrease
activity
any
lysosomal
enzymes.
Here,
we
discuss
pathomechanisms
MPSPS,
comparing
them
those
MPS.
Moreover,
asked
question
whether
should
be
classified
type
MPS
or
separate
disease,
contrary
‘classical’
types,
despite
GAG
accumulation,
no
enzymes
responsible
for
degradation
these
compounds
could
detected
MPSPS.
molecular
mechanism
appearance
suggested
on
basis
results
available
literature.
Язык: Английский
Body Height of MPS I and II Patients after Hematopoietic Stem Cell Transplantation: The Impact of Dermatan Sulphate
Diagnostics,
Год журнала:
2024,
Номер
14(17), С. 1956 - 1956
Опубликована: Сен. 4, 2024
Introduction:
Hematopoietic
stem
cell
transplantation
(HSCT)
comprises
one
of
the
two
main
treatment
regimens
for
patients
with
mucopolysaccharidoses
(MPS).
There
is
a
scarcity
literature
concerning
process
growth
in
children
Mucopolysaccharidosis
type
I
(MPS
I)
and
II)
after
HSCT.
The
aim
this
manuscript
was
to
evaluate
therapeutic
effect
HSCT
on
heights
MPS
II.
Material
methods:
It
an
observational,
single-center
study
II
treated
Results:
6
patients,
including
4
2
II,
underwent
at
median
age
years.
All
are
alive
date,
7.7
years
(range
5.5–12
years)
last
follow-up.
In
both
groups
HSCT,
rate
higher
than
untreated
found
be
line
population
norm.
who
were
normalization
urinary
GAG
excretion
observed.
Additionally,
no
bands
DS
HS
electrophoresis
visible.
Conclusions:
Both
presented
height
gain
compared
curves
patients.
absence
dermatan
sulphate
could
lead
normal
bone
length.
Язык: Английский
Alterations in Hurler–Scheie Syndrome Revealed by Mass Spectrometry-Based Proteomics and Phosphoproteomics Analysis
OMICS A Journal of Integrative Biology,
Год журнала:
2024,
Номер
28(11), С. 548 - 562
Опубликована: Окт. 29, 2024
Hurler-Scheie
syndrome
(MPS
IH/S),
also
known
as
mucopolysaccharidosis
type
I-H/S
is
a
lysosomal
storage
disorder
caused
by
deficiency
of
the
enzyme
alpha-L-iduronidase
(IDUA)
leading
to
accumulation
glycosaminoglycans
(GAGs)
in
various
tissues,
resulting
wide
range
symptoms
affecting
different
organ
systems.
Postgenomic
omics
technologies
offer
promise
understand
changes
proteome,
phosphoproteome,
and
phosphorylation-based
signaling
MPS
IH/S.
Accordingly,
we
report
here
large
dataset
proteomic
phosphoproteomic
analyses
fibroblasts
derived
from
patients
with
IH/S
(
Язык: Английский