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.
Inherited
retinal
degenerations
(IRDs)
constitute
a
group
of
clinically
and
genetically
diverse
vision-impairing
disorders.
Retinitis
pigmentosa
(RP),
the
most
common
form
IRD,
is
characterized
by
gradual
dysfunction
degeneration
rod
photoreceptors,
followed
loss
cone
photoreceptors.
Recently,
we
identified
reserpine
as
lead
molecule
for
maintaining
survival
in
mouse
human
organoids
well
rd16
mouse,
which
phenocopy
Leber
congenital
amaurosis
caused
mutations
cilia-centrosomal
gene
CEP290
(Chen
et
al.,
2023).
Here,
show
therapeutic
potential
rhodopsin
P23H
rat
model
autosomal
dominant
RP.
At
postnatal
day
(P)
68,
when
males
females
are
analyzed
together,
reserpine-treated
rats
exhibit
higher
rod-derived
scotopic
b-wave
amplitudes
compared
to
controls
with
little
or
no
change
a-wave
cone-derived
photopic
b-wave.
Interestingly,
female
display
enhanced
a-
b-waves
responses
at
P68,
along
better
contrast
threshold
increased
outer
nuclear
layer
thickness.
The
demonstrate
preservation
both
photoreceptors
following
treatment.
Retinal
transcriptome
analysis
reveals
sex-specific
reserpine,
significant
upregulation
phototransduction
genes
proteostasis-related
pathways,
notably,
associated
stress
response.
This
study
builds
upon
our
previously
reported
results
reaffirming
gene-agnostic
treatment
IRDs
emphasizes
importance
biological
sex
disease
research
therapy
development.
PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(5), P. e0321867 - e0321867
Published: May 16, 2025
The
many
layers
of
the
neuroretina
contain
a
complex,
interconnected
network
specialized
neurons
that
both
process
visual
stimuli
and
conduct
processed
information
to
higher
brain
areas.
Neural
networks
rely
on
proteostatic
control
mechanisms
maintain
proper
protein
homeostasis
in
cell
bodies
as
well
within
synapses;
chaperones
play
an
important
role
regulating
supporting
this
process.
ProSAAS
is
small
neuronal
chaperone
functions
anti-aggregant
vitro
assays
released
upon
depolarization
primary
cultures.
We
here
report
potential
for
proSAAS
retina.
A
review
human
mouse
retinal
RNAseq
studies
reveals
expression
abundant
Single
sequencing
data
from
show
levels
are
highest
ganglion
cells
(RGCs)
horizontal
cells.
Using
antibodies
combination
with
antisera
known
markers
sections,
we
confirm
showing
RGCs
signal
concentrated
layer
inner
plexiform
layer,
dense
synaptic
connecting
neurons.
Western
blotting
extracts
indicates
presence
two
forms,
21
kDa
C-terminally
form,
13
species
which,
based
antibody
specificity,
likely
represents
internal
fragment.
This
fragment
also
found
prepared
retinas.
Taken
together,
our
provide
support
hypothesis
synapses
utilize
signaling.
Aging,
Journal Year:
2023,
Volume and Issue:
15(10), P. 4498 - 4509
Published: May 28, 2023
To
investigate
the
expression
of
αA-crystallin
(CRYAA)
in
age-related
cataract
(ARC)
models
and
its
role
lens
epithelial
cells
(LECs).We
used
Flow
cytometry
to
detect
apoptosis
cell
cycle
HLEB3
Real-time
fluorescence
quantitative
polymerase
chain
reaction
CRYAA
mRNA
rabbit
lens.
The
lenses
as
well
proteins
related
autophagy
transfected
were
detected
by
western
blotting.
structure
rabbits
was
investigated
using
hematoxylin-eosin
staining.
Protein
thermostability
assay
performed
thermal
stability
proteins.
CCK-
8
viability
cells,
transfection
recorded
photography.Hydrogen
peroxide
can
promote
arrest
naphthalene
cause
formation
damage
rabbits.
Both
ARC
reduce
CRYAA.
silencing
increased
cells.
Therapeutic Delivery,
Journal Year:
2024,
Volume and Issue:
15(6), P. 463 - 480
Published: June 2, 2024
Ophthalmic
diseases
can
result
in
permanent
vision
loss
and
blindness.
Convenient
topical
systemic
treatments
are
preferred
to
address
these
sight-threatening
conditions.
However,
the
unique
anatomy
of
eye
presents
challenges
for
drug
delivery.
Various
ophthalmic
ointment
formulations
have
been
developed
enhance
bioavailability
prolong
residence
time
improve
corneal
permeability.
This
article
explores
a
wide
range
ocular
affecting
individuals
globally
how
ointments
used
manage
them.
From
barriers,
this
review
focuses
on
published
scientific
research
formulation
strategies
severe
complications
using
conventional
ointments.
Additionally,
it
delves
through
patented
technologies
marketed
supporting
use
Human Molecular Genetics,
Journal Year:
2024,
Volume and Issue:
33(10), P. 860 - 871
Published: Feb. 7, 2024
Abstract
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.
Journal of Inflammation Research,
Journal Year:
2024,
Volume and Issue:
Volume 17, P. 3433 - 3448
Published: May 1, 2024
Abstract:
As
one
of
the
most
prevalent
chronic
inflammatory
skin
diseases,
atopic
dermatitis
(AD)
increasingly
affects
aging
population.
Amid
ongoing
global
trend,
it's
essential
to
recognize
intricate
relationship
between
AD
and
aging.
This
paper
reviews
existing
knowledge,
summarizing
clinical
observations
associations
aging-related
diseases
in
various
systems,
including
endocrine,
cardiovascular,
neurological.
Additionally,
it
discusses
major
theories
explaining
correlation,
encompassing
skin-mucosal
barriers,
systemic
inflammation
stress,
genes,
signal
transduction,
environmental
behavioral
factors.
The
association
holds
significant
importance,
both
population
basic
perspectives.
While
further
research
is
warranted,
this
aims
inspire
deeper
exploration
inflammation/allergy-aging
dynamics
timely
management
elderly
patients
with
AD.
Keywords:
dermatitis,
aging,
age-related
observations,
mechanical
Frontiers in Bioscience-Landmark,
Journal Year:
2024,
Volume and Issue:
29(7)
Published: July 22, 2024
Retinal
degeneration
(RD)
is
a
group
of
chronic
blinding
diseases
characterised
by
progressive
retinal
cell
death.
As
the
disease
progresses,
vision
deteriorates
due
to
death
and
impaired
integrity,
eventually
leading
complete
loss
vision.
Therefore,
function
environmental
homeostasis
retina
have
an
important
impact
on
pathogenesis
treatment
RD.
Ubiquitination,
as
complex
post-translational
modification
process,
plays
essential
role
in
maintaining
normal
function.
It
covalently
combines
ubiquitin
with
protein
through
series
enzyme-mediated
reactions,
participates
processes
such
gene
transcription,
cycle
DNA
repair,
apoptosis
immune
response.
At
same
time,
it
central
degradation.
There
are
two
major
degradation
systems
eukaryotic
cells:
ubiquitin-proteasome
system
autophagy-lysosomal
system.
The
pathway
maintains
reducing
abnormal
accumulation
modes
Either
dysregulation
ubiquitination
or
disruption
may
lead
development
This
article
aims
comprehensively
review
recent
research
progress
ubiquitin-related
genes,
proteins
RD,
summarize
potential
targeted
therapy
strategies
for
it.
expected
provide
valuable
guidance
further
application
Biomolecules,
Journal Year:
2023,
Volume and Issue:
13(4), P. 693 - 693
Published: April 19, 2023
Recent
advances
in
next-generation
sequencing
and
data
analysis
have
provided
new
gateways
for
identification
of
novel
genome-wide
genetic
determinants
governing
tissue
development
disease.
These
revolutionized
our
understanding
cellular
differentiation,
homeostasis,
specialized
function
multiple
tissues.
Bioinformatic
functional
these
the
pathways
they
regulate
a
basis
design
experiments
to
answer
wide
range
long-sought
biological
questions.
A
well-characterized
model
application
emerging
technologies
is
differentiation
ocular
lens
how
individual
morphogenesis,
gene
expression,
transparency,
refraction.
applications
on
chicken
mouse
models
using
variety
omics
techniques
including
RNA-seq,
ATAC-seq,
whole-genome
bisulfite
(WGBS),
chip-seq,
CUT&RUN
revealed
essential
chromatin
features
structure
function.
Multiomics
integration
has
established
functions
processes
formation,
transparency
transcription
control
pathways,
autophagy
remodeling
signal
transduction
among
others.
This
review
summarizes
recent
applied
lens,
methods
integrating
multiomics
data,
advanced
biology
The
approach
are
relevant
identifying
requirements
more
complex
tissues
disease
states.
