Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 21, 2023
Abstract
The
recovery
of
mitochondrial
quality
control
(MQC)
may
bring
innovative
solutions
for
neuroprotection,
while
also
imposing
an
extraordinary
challenge
given
the
need
holistic
approaches
to
restore
dynamics
(fusion/fission)
and
turnover
(mitophagy
biogenesis).
In
Diabetic
Retinopathy
(DR)
this
therapeutic
approach
is
further
compounded
by
our
lack
understanding
human
retinal
neurodegeneration,
but
how
MQC
processes
interplay
during
disease
progression.
Here,
we
show
first
time
that
mitochondria
remodel
towards
hyperfusion
neurodegeneration
in
murine
diabetes.
Using
Mito-QC
reporter,
demonstrate
blunts
homeostatic
diabetes,
causing
metabolic,
neuronal,
neuro-inflammatory
(glial)
stress.
By
mimicking
remodelling
vitro
,
generated
a
drug
discovery
platform
whereby
glycosylated
N6-furfuryladenine(s)
(but
not
other
PINK1-activators)
restored
cellular
bioenergetics
relaxing
controlled
fashion.
Oral
administration
N6-furfuryladenine
(Ins2
Akita
)
diabetic
retina,
improving
clinical
correlates
(electroretinogram
SD-OCT)
conferring
human-relevant
neuroprotection
regardless
glycaemic
status.
Collectively,
study
provides
new
translational
insights
retina
through
MQC.
Intercellular
communication
is
pivotal
in
mediating
the
transfer
of
mitochondria
from
donor
to
recipient
cells.
This
process
orchestrates
various
biological
functions,
including
tissue
repair,
cell
proliferation,
differentiation
and
cancer
invasion.
Typically,
dysfunctional
depolarized
are
eliminated
through
intracellular
or
extracellular
pathways.
Nevertheless,
increasing
evidence
suggests
that
intercellular
damaged
associated
with
pathogenesis
diverse
diseases.
review
investigates
prevalent
triggers
mitochondrial
damage
underlying
mechanisms
transfer,
elucidates
role
directional
both
physiological
pathological
contexts.
Additionally,
we
propose
potential
previously
unknown
explore
their
prospective
roles
disease
prevention
therapy.
To
clarify
our
understanding
of
glial
phagocytosis
in
retinal
development,
we
used
real-time
imaging
larval
zebrafish
to
provide
cell-type
specific
resolution
this
process.
We
show
that
radial
Müller
glia
frequently
participate
microglial
while
also
completing
a
subset
phagocytic
events.
actively
engage
with
dying
cells
through
initial
target
cell
contact
and
cup
formation,
after
which
an
exchange
the
from
microglia
often
takes
place.
In
addition,
find
evidence
cellular
material,
possibly
cup,
is
internalized
into
compartments.
Previously
undescribed
behaviors
were
seen,
including
cargo
splitting,
wrestling
for
targets
lateral
passing
neighbors.
Collectively,
work
provides
new
insight
functions
intercellular
interactions,
will
allow
future
understand
these
on
molecular
level.
International Immunopharmacology,
Год журнала:
2024,
Номер
134, С. 112193 - 112193
Опубликована: Май 8, 2024
Retinal
neurodegenerative
diseases
are
a
category
of
refractory
blinding
eye
conditions
closely
associated
with
oxidative
stress
induced
by
mitochondrial
dysfunction
in
retinal
cells.
SARM1,
core
driver
molecule
leading
to
axonal
degeneration,
possesses
NAD
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 6, 2024
The
recovery
of
mitochondrial
quality
control
(MQC)
may
bring
innovative
solutions
for
neuroprotection,
while
imposing
a
significant
challenge
given
the
need
holistic
approaches
to
restore
dynamics
(fusion/fission)
and
turnover
(mitophagy
biogenesis).
In
diabetic
retinopathy,
this
is
compounded
by
our
lack
understanding
human
retinal
neurodegeneration,
but
also
how
MQC
processes
interact
during
disease
progression.
Here,
we
show
that
mitochondria
hyperfusion
characteristic
neurodegeneration
in
murine
diabetes,
blunting
homeostatic
causing
metabolic
neuro-inflammatory
stress.
By
mimicking
remodelling
vitro,
ascertain
N6-furfuryladenosine
enhances
bioenergetics
relaxing
controlled
fashion.
Oral
administration
mouse
retina
(Ins2Akita
males),
improving
clinical
correlates
conferring
neuroprotection
regardless
glycaemic
status.
Our
findings
provide
translational
insights
through
MQC.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 12, 2025
Abstract
Zebrafish
is
a
popular
species
widely
used
in
vision
research.
The
zebrafish
retina
has
one
rod
and
four
cone
subtypes
(UV-,
blue-,
green-,
red-sensitive)
with
40%-rod
60%-cone
ratio,
making
it
suitable
for
comparable
studies
of
rods
cones
health
disease.
However,
the
basic
photoresponse
properties
have
not
been
described
yet.
Here,
we
established
method
collecting
flash
photoresponses
from
by
recording
membrane
current
suction
electrode.
Photoreceptor
could
be
distinguished
based
on
their
characteristic
morphology
spectral
sensitivity.
Rods
showed
40–220-fold
higher
photosensitivity
than
cones.
In
subtypes,
green-sensitive
highest
sensitivity,
5.5-fold
that
red
Unexpectedly,
produced
smaller
responses
despite
larger
outer
segments.
Dim
response
analysis
quickest
kinetics
blue-
red-sensitive
cones,
about
2-fold
faster
UV-
6.6-fold
responses.
We
also
obtained
pharmacologically
isolated
photoreceptor
voltage
(a-wave)
retinas
using
ex
vivo
electroretinography
(ERG).
flashes
evoked
rod-only
responses,
while
bright
two-component
slow
component
fast
component.
Red-
were
dominant
sources
overall
response.
These
provide
foundation
use
to
study
fundamental
mechanisms
modulate
function
vertebrate
photoreceptors
Translational Neurodegeneration,
Год журнала:
2025,
Номер
14(1)
Опубликована: Апрель 16, 2025
Abstract
Heterozygous
mutations
in
GRN
gene
lead
to
insufficient
levels
of
the
progranulin
(PGRN)
protein,
resulting
frontotemporal
dementia
(FTD)
with
TAR
DNA-binding
protein
43
(TDP-43)
inclusions,
classified
pathologically
as
lobar
degeneration
(FTLD-TDP).
Homozygous
are
exceedingly
rare
and
cause
neuronal
ceroid
lipofuscinosis
11,
a
lysosomal
storage
disease
onset
young
adulthood,
or
an
FTD
syndrome
late-onset
manifestations.
In
this
review,
we
highlight
broad
spectrum
clinical
phenotypes
associated
PGRN
deficiency,
including
primary
progressive
aphasia
behavioral
variant
dementia.
We
explore
these
alongside
relevant
rodent
vitro
human
models,
ranging
from
induced
pluripotent
stem
cell-derived
neural
progenitors,
neurons,
microglia,
astrocytes
genetically
engineered
heterotypic
organoids
containing
both
neurons
astrocytes.
summarize
advantages
limitations
models
recapitulating
main
FTLD-
hallmarks,
highlighting
role
non-cell-autonomous
mechanisms
formation
TDP-43
pathology,
neuroinflammation,
neurodegeneration.
Data
obtained
patients’
brain
tissues
biofluids,
parallel
single-cell
transcriptomics,
demonstrate
complexity
interactions
among
highly
heterogeneous
cellular
clusters
present
brain,
astrocytes,
oligodendroglia,
endothelial
cells,
pericytes.
Emerging
evidence
has
revealed
that
deficiency
is
cell
cluster-specific,
often
conserved,
genetic
molecular
central
nervous
system.
focus
on
how
distinct
populations
their
dysfunctional
crosstalk
contribute
neurodegeneration
neuroinflammation
FTD-
.
Specifically,
characterize
lipid
droplet-accumulating
microglia
alterations
myelin
content
dysfunction
caused
by
deficiency.
Additionally,
consider
deregulation
glia-neuron
communication
affects
exchange
organelles
such
mitochondria,
removal
excess
toxic
products
aggregates,
PGRN-related
