Brain,
Journal Year:
2023,
Volume and Issue:
147(3), P. 970 - 979
Published: Oct. 26, 2023
Abstract
Frontotemporal
dementia
(FTD)
and
amyotrophic
lateral
sclerosis
(ALS)
are
two
incurable
neurodegenerative
diseases
that
exist
on
a
clinical,
genetic
pathological
spectrum.
The
VCP
gene
is
highly
relevant,
being
directly
implicated
in
both
FTD
ALS.
Here,
we
investigate
the
effects
of
mutations
cellular
homoeostasis
human
induced
pluripotent
stem
cell-derived
cortical
neurons,
focusing
endolysosomal
biology
tau
pathology.
We
found
cause
abnormal
accumulation
enlarged
endolysosomes
accompanied
by
impaired
interaction
between
nuclear
RNA
binding
proteins:
fused
sarcoma
(FUS)
splicing
factor,
proline-
glutamine-rich
(SFPQ)
neurons.
spatial
dissociation
intranuclear
FUS
SFPQ
correlates
with
alternative
MAPT
pre-mRNA
increased
phosphorylation.
Importantly,
show
inducing
4R
expression
using
antisense
oligonucleotide
technology
sufficient
to
drive
neurodegeneration
control
which
phenocopies
VCP-mutant
In
summary,
our
findings
demonstrate
hyperphosphorylation,
dysfunction,
lysosomal
membrane
rupture,
endoplasmic
reticulum
stress
apoptosis
driven
pathogenic
increase
tau.
Translational Neurodegeneration,
Journal Year:
2025,
Volume and Issue:
14(1)
Published: April 16, 2025
Abstract
Amyotrophic
lateral
sclerosis
(ALS)
is
a
fatal
motor
neuron
disease
that
remains
incurable.
Although
the
etiologies
of
ALS
are
diverse
and
precise
pathogenic
mechanisms
not
fully
understood,
approximately
20%
cases
caused
by
genetic
factors.
Therefore,
advancing
targeted
gene
therapies
holds
significant
promise,
at
least
for
patients
with
etiologies.
In
this
review,
we
summarize
main
strategies
techniques
current
based
on
risk
genes,
review
recent
findings
from
animal
studies
clinical
trials.
Additionally,
highlight
ALS-related
genes
well-understood
potential
numerous
emerging
gene-targeted
therapeutic
approaches
ALS.
Human Molecular Genetics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 30, 2025
Abstract
Neurodegenerative
disorders
(NDDs),
characterized
by
a
progressive
loss
of
neurons
and
cognitive
function,
are
severe
burden
to
human
health
mental
fitness
worldwide.
A
hallmark
NDDs
such
as
Alzheimer’s
disease,
Huntington’s
Parkinson’s
disease
(PD),
amyotrophic
lateral
sclerosis
(ALS)
prion
diseases
is
disturbed
cellular
proteostasis,
resulting
in
pathogenic
deposition
aggregated
protein
species.
Autophagy
major
process
maintaining
proteostasis
integral
innate
immune
defenses
that
mediates
lysosomal
turnover.
Defects
autophagy
thus
frequently
associated
with
NDDs.
In
this
review,
we
discuss
the
interplay
between
proteins
provide
an
overview
over
recent
discoveries
inborn
errors
canonical
While
mutations
receptors
seems
be
mainly
development
ALS,
mitophagy
found
promote
PD.
Finally,
argue
whether
may
impact
progress
onset
well
potential
targeting
therapeutic
approach.
Concludingly,
understanding
due
autophagy—“autophagopathies”—will
help
unravel
underlying
NDD
pathomechanisms
unique
insights
into
neuroprotective
role
autophagy,
potentially
paving
way
for
novel
interventions.
The Journal of Biochemistry,
Journal Year:
2023,
Volume and Issue:
175(2), P. 141 - 146
Published: Nov. 8, 2023
Abstract
Cellular
zoning
or
partitioning
is
critical
in
preventing
macromolecules
from
random
diffusion
and
orchestrating
the
spatiotemporal
dynamics
of
biochemical
reactions.
Along
with
membranous
organelles,
membraneless
organelles
contribute
to
precise
regulation
reactions
inside
cells.
In
response
environmental
cues,
rapidly
form
through
liquid–liquid
phase
separation,
sequester
certain
proteins
RNAs,
mediate
specific
dissociate.
Among
ubiquitin-positive
condensates,
namely,
p62
bodies,
maintain
cellular
homeostasis
selective
autophagy
themselves
intracellular
quality
control.
bodies
also
activate
anti-oxidative
stress
regulated
by
KEAP1-NRF2
system.
this
review,
we
present
an
overview
recent
advancements
molecular
biology
related
highlighting
their
dynamic
nature
functions.
Brain,
Journal Year:
2023,
Volume and Issue:
147(3), P. 970 - 979
Published: Oct. 26, 2023
Abstract
Frontotemporal
dementia
(FTD)
and
amyotrophic
lateral
sclerosis
(ALS)
are
two
incurable
neurodegenerative
diseases
that
exist
on
a
clinical,
genetic
pathological
spectrum.
The
VCP
gene
is
highly
relevant,
being
directly
implicated
in
both
FTD
ALS.
Here,
we
investigate
the
effects
of
mutations
cellular
homoeostasis
human
induced
pluripotent
stem
cell-derived
cortical
neurons,
focusing
endolysosomal
biology
tau
pathology.
We
found
cause
abnormal
accumulation
enlarged
endolysosomes
accompanied
by
impaired
interaction
between
nuclear
RNA
binding
proteins:
fused
sarcoma
(FUS)
splicing
factor,
proline-
glutamine-rich
(SFPQ)
neurons.
spatial
dissociation
intranuclear
FUS
SFPQ
correlates
with
alternative
MAPT
pre-mRNA
increased
phosphorylation.
Importantly,
show
inducing
4R
expression
using
antisense
oligonucleotide
technology
sufficient
to
drive
neurodegeneration
control
which
phenocopies
VCP-mutant
In
summary,
our
findings
demonstrate
hyperphosphorylation,
dysfunction,
lysosomal
membrane
rupture,
endoplasmic
reticulum
stress
apoptosis
driven
pathogenic
increase
tau.
