Methodist DeBakey Cardiovascular Journal,
Journal Year:
2023,
Volume and Issue:
19(5), P. 16 - 25
Published: Jan. 1, 2023
Cardiovascular
diseases
are
the
number
one
cause
of
death
worldwide
and
in
United
States
(US).
frequently
progress
to
end-stage
heart
failure,
curative
therapies
extremely
limited.
Intense
interest
has
focused
on
deciphering
cascades
networks
that
govern
cardiomyocyte
proliferation
regeneration
injured
heart.
For
example,
studies
have
shown
lower
organisms
such
as
adult
newt
zebrafish
capacity
completely
regenerate
their
with
restoration
function.
Similarly,
neonatal
mouse
pig
also
able
myocardium
due
from
preexisting
cardiomyocytes.
Using
these
animal
models
transcriptome
analyses,
efforts
definition
factors
signaling
pathways
can
reactivate
induce
mammalian
These
discoveries
potential
define
novel
promote
repair
injured,
Brain Communications,
Journal Year:
2024,
Volume and Issue:
6(3)
Published: Jan. 1, 2024
Friedreich's
ataxia
is
a
neurodegenerative
disorder
caused
by
reduced
frataxin
levels.
It
leads
to
motor
and
sensory
impairments
has
median
life
expectancy
of
around
35
years.
As
the
most
common
inherited
form
ataxia,
lacks
reliable,
non-invasive
biomarkers,
prolonging
inflating
cost
clinical
trials.
This
study
proposes
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 25, 2023
Abstract
Friedreich’s
Ataxia
(FRDA)
is
a
neurodegenerative
disorder
caused
by
reduced
frataxin
(FXN)
levels.
It
leads
to
motor
and
sensory
impairments
has
median
life
expectancy
of
around
35
years.
As
the
most
common
inherited
form
ataxia
with
no
cure,
FRDA
lacks
reliable,
non-invasive
biomarkers,
prolonging
inflating
cost
clinical
trials.
This
study
identifies
long
non-coding
RNA
Tug1
as
potential
blood-based
biomarker.
In
previous
using
knockdown
mouse
model
(FRDAkd),
we
observed
several
hallmark
symptoms
abnormalities
in
various
tissues.
Building
on
this,
hypothesized
that
dual-source
approach—comparing
data
from
peripheral
blood
samples
patients
tissue
affected
areas
FRDAkd
mice,
tissues
usually
unattainable
patients—would
effectively
identify
robust
biomarkers.
A
comprehensive
reanalysis
was
conducted
gene
expression
183
age-
sex-matched
patients,
carriers,
controls,
well
192
datasets
mice.
Blood
underwent
isolation
qRT-PCR,
confirmed
through
ELISA.
interaction
explored
via
pull-down
assays.
Validation
performed
serum
an
independent
set
45
healthy
patients;
66
heterozygous
72
patients.
Slc40a1
emerged
(One-way
ANOVA,
p
≤
0.05).
consistently
downregulated
after
Fxn
correlated
strongly
levels
(R
2
=
0.71
during
depletion,
R
0.74
rescue).
showed
similar
but
tissue-specific
pattern.
Further
validation
Tug1’s
downstream
targets
strengthened
its
biomarker
candidacy.
additional
human
samples,
TUG1
were
significantly
both
whole
compared
controls
(Wilcoxon
signed-rank
test,
<
Regression
analyses
revealed
negative
correlation
between
disease
onset
(p
0.0037),
positive
correlations
duration
Functional
Disability
Stage
score
0.04).
suggests
elevated
correlate
earlier
more
severe
cases.
summary,
this
highlights
crucial
for
FRDA.
consistent
variance
across
closely
associated
severity
key
pathways.
also
correlates
levels,
making
it
promising
early,
marker.
offers
monitoring
therapeutic
development,
warranting
further
research.
Methodist DeBakey Cardiovascular Journal,
Journal Year:
2023,
Volume and Issue:
19(5), P. 16 - 25
Published: Jan. 1, 2023
Cardiovascular
diseases
are
the
number
one
cause
of
death
worldwide
and
in
United
States
(US).
frequently
progress
to
end-stage
heart
failure,
curative
therapies
extremely
limited.
Intense
interest
has
focused
on
deciphering
cascades
networks
that
govern
cardiomyocyte
proliferation
regeneration
injured
heart.
For
example,
studies
have
shown
lower
organisms
such
as
adult
newt
zebrafish
capacity
completely
regenerate
their
with
restoration
function.
Similarly,
neonatal
mouse
pig
also
able
myocardium
due
from
preexisting
cardiomyocytes.
Using
these
animal
models
transcriptome
analyses,
efforts
definition
factors
signaling
pathways
can
reactivate
induce
mammalian
These
discoveries
potential
define
novel
promote
repair
injured,
