bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 8, 2024
Neuromuscular
disorders
caused
by
dysfunction
of
the
mitochondrial
respiratory
chain
are
common,
severe
and
untreatable.
We
recovered
a
number
genes,
including
electron
transport
components,
in
large
forward
genetic
screen
for
mutations
causing
age-related
neurodegeneration
context
proteostasis
dysfunction.
created
model
complex
I
deficiency
Drosophila
retina
to
probe
role
protein
degradation
abnormalities
encephalomyopathies.
Using
our
model,
we
found
that
regulates
both
ubiquitin/proteasome
autophagy/lysosome
arms
machinery.
further
performed
an
vivo
kinome
uncover
new
potentially
druggable
mechanisms
contributing
related
failure.
Reduction
RIOK
kinases
innate
immune
signaling
kinase
pelle
prevented
animals.
Genetically
targeting
oxidative
stress,
but
not
RIOK1
or
knockdown,
normalized
markers.
Our
findings
outline
distinct
pathways
controlling
introduce
experimentally
facile
which
study
these
debilitating
currently
treatment-refractory
disorders.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(11), P. e0313446 - e0313446
Published: Nov. 11, 2024
Glaucoma,
characterized
by
a
high
incidence
and
significant
ocular
harm,
has
been
elucidated
through
various
mechanisms.
Excessive
autophagy
leading
to
the
loss
of
retinal
ganglion
cells
(RGCs)
is
suggested
as
one
potential
cause
for
visual
impairment
in
glaucoma.
Human Molecular Genetics,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 12, 2024
Genome-wide
association
studies
have
uncovered
mostly
non-coding
variants
at
over
60
genetic
loci
linked
to
susceptibility
for
age-related
macular
degeneration
(AMD).
To
ascertain
the
causal
gene
PILRB/PILRA
locus,
we
used
a
CRISPR
strategy
produce
germline
deletions
in
mouse
paired
immunoglobin-like
type
2
receptor
(Pilr)
genes
that
encode
highly
related
activating
(PILRB)
and
inhibitory
(PILRA)
receptors.
We
show
combined
loss
of
Pilrb1
Pilrb2,
but
not
Pilra,
leads
an
early
relatively
stationary
defect
as
electroretinography
(ERG)
amplitudes
Pilrb1/2-/-
mice
exhibit
marked
reduction
postnatal
day
15
do
additional
significant
decrease
3
12-months.
No
alterations
are
evident
Müller
glia,
microglia,
bipolar,
amacrine
horizontal
cells
based
on
immunohistochemistry
using
cell-type
specific
markers.
PILRB
immunostaining
is
specifically
detected
proximal
part
photoreceptor
outer
segment.
Reduced
expression
select
calcium-regulated
phototransduction
synapse-associated
proteins,
including
GCAP1
2,
PDE6b,
AIPL1,
PSD95,
CTBP1
indicates
dysregulation
calcium
homeostasis
possible
mechanism
retinal
phenotype
mice.
Our
suggest
novel
function
photoreceptors
PILRB,
PILRA,
with
AMD
pathogenesis.
Cells,
Journal Year:
2023,
Volume and Issue:
12(19), P. 2333 - 2333
Published: Sept. 22, 2023
The
biological
mechanisms
linking
sedentary
lifestyles
and
metabolic
derangements
are
incompletely
understood.
In
this
study,
temporal
muscle
inactivation
in
Drosophila
larvae
carrying
a
temperature-sensitive
mutation
the
shibire
(shi1)
gene
was
induced
to
mimic
behavior
during
early
life
study
its
transcriptional
outcome.
Our
findings
indicated
significant
change
epigenetic
profile,
as
well
genomic
of
RNA
Pol
II
binding
inactive
muscles
relative
control,
within
relatively
short
time
period.
Whole-genome
analysis
RNA-Pol
DNA
by
muscle-specific
targeted
DamID
(TaDa)
protocol
revealed
that
inactivity
altered
121
out
2010
genes
(6%),
with
three-fold
enrichment
coding
for
lncRNAs.
suppressed
protein-coding
included
associated
longevity,
repair,
function,
ubiquitin-dependent
proteostasis.
Moreover,
inducing
exerted
multi-level
impact
upon
chromatin
modifications,
triggering
an
balance
active
versus
marks.
downregulated
essential
structure
carbohydrate
metabolism,
others.
Given
multiple
analogous
many
human
genes,
extrapolating
our
humans
may
hold
promise
establishing
molecular
link
between
diseases.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 8, 2024
Neuromuscular
disorders
caused
by
dysfunction
of
the
mitochondrial
respiratory
chain
are
common,
severe
and
untreatable.
We
recovered
a
number
genes,
including
electron
transport
components,
in
large
forward
genetic
screen
for
mutations
causing
age-related
neurodegeneration
context
proteostasis
dysfunction.
created
model
complex
I
deficiency
Drosophila
retina
to
probe
role
protein
degradation
abnormalities
encephalomyopathies.
Using
our
model,
we
found
that
regulates
both
ubiquitin/proteasome
autophagy/lysosome
arms
machinery.
further
performed
an
vivo
kinome
uncover
new
potentially
druggable
mechanisms
contributing
related
failure.
Reduction
RIOK
kinases
innate
immune
signaling
kinase
pelle
prevented
animals.
Genetically
targeting
oxidative
stress,
but
not
RIOK1
or
knockdown,
normalized
markers.
Our
findings
outline
distinct
pathways
controlling
introduce
experimentally
facile
which
study
these
debilitating
currently
treatment-refractory
disorders.
