Frontiers in Molecular Neuroscience,
Год журнала:
2024,
Номер
17
Опубликована: Ноя. 25, 2024
Central
to
the
process
of
axon
elongation
is
concept
compartmentalized
signaling,
which
involves
A-kinase
anchoring
protein
(AKAP)-dependent
organization
signaling
pathways
within
distinct
subcellular
domains.
This
spatial
also
critical
for
translating
electrical
activity
into
biochemical
events.
Despite
intensive
research,
detailed
mechanisms
by
separation
governs
axonal
outgrowth
and
pathfinding
remain
unresolved.
In
this
study,
we
demonstrate
that
mAKAPα
(AKAP6),
located
in
perinuclear
space
primary
hippocampal
neurons,
scaffolds
calcineurin,
NFAT,
MEF2
transcription
factors
activity-dependent
elongation.
By
employing
disruptors,
show
mAKAPα/calcineurin/MEF2
pathway,
but
not
drives
outgrowth.
Furthermore,
mAKAPα-controlled
linked
changes
expression
genes
involved
Ca
Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Сен. 21, 2023
Retinal
ganglion
cell
(RGC)
death
in
glaucoma
and
other
optic
neuropathies
results
irreversible
vision
loss
due
to
the
mammalian
central
nervous
system's
limited
regenerative
capacity.
RGC
repopulation
is
a
promising
therapeutic
approach
reverse
from
if
newly
introduced
neurons
can
reestablish
functional
retinal
thalamic
circuits.
In
theory,
RGCs
might
be
repopulated
through
transplantation
of
stem
cell-derived
or
via
induction
endogenous
transdifferentiation.
The
Repopulation,
Stem
Cell
Transplantation,
Optic
Nerve
Regeneration
(RReSTORe)
Consortium
was
established
address
challenges
associated
with
repair
visual
pathway
neuropathy.
2022,
RReSTORe
initiated
ongoing
international
collaborative
discussions
advance
field
has
identified
five
critical
areas
focus:
(1)
development
differentiation,
(2)
Transplantation
methods
models,
(3)
survival,
maturation,
host
interactions,
(4)
Inner
wiring,
(5)
Eye-to-brain
connectivity.
Here,
we
discuss
most
pertinent
questions
that
exist
on
path
clinical
translation
suggest
experimental
directions
propel
this
work
going
forward.
Using
these
subtopic
discussion
groups
(SDGs)
as
framework,
multidisciplinary
approaches
restore
diseased
by
leveraging
groundbreaking
insights
developmental
neuroscience,
biology,
molecular
optical
imaging,
animal
models
neuropathy,
immunology
&
immunotolerance,
neuropathology
neuroprotection,
materials
science
biomedical
engineering,
neuroscience.
While
significant
hurdles
remain,
Consortium's
efforts
provide
comprehensive
roadmap
for
advancing
hold
potential
transformative
progress
restoring
patients
suffering
neuropathies.
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(11), С. 4382 - 4406
Опубликована: Янв. 1, 2024
Mitophagy
selectively
eliminates
damaged
or
dysfunctional
mitochondria,
playing
a
crucial
role
in
maintaining
mitochondrial
quality
control.
However,
it
remains
unclear
whether
mitophagy
can
be
fully
activated
and
how
evolves
after
SCI.
Our
RNA-seq
analysis
of
animal
samples
from
sham
1,
3,
5,
7
days
post-SCI
indicated
that
was
indeed
inhibited
during
the
acute
subacute
early
stages.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 4, 2025
Mechanisms
underlying
functional
axonal
rewiring
after
adult
mammalian
central
nervous
system
(CNS)
injuries
remain
unclear
partially
due
to
limited
models.
Here
we
develop
a
mouse
intracranial
pre-olivary
pretectal
nucleus
(OPN)
optic
tract
injury
model
and
demonstrate
that
Pten/Socs3
knockout
CNTF
expression
in
retinal
ganglion
cells
(RGCs)
promotes
regeneration
OPN
reinnervation.
Revealed
by
transmission
electron
microscopy,
trans-synaptic
labeling,
electrophysiology,
synapses
are
formed
mainly
intrinsically
photosensitive
RGCs,
thereby
restoring
the
pupillary
light
reflex
(PLR).
Moreover,
combining
with
Lipin1
knockdown
accelerates
recovery
achieves
reconnection
chronic
injury.
PLR
can
be
further
boosted
increasing
RGC
photosensitivity
melanopsin
overexpression,
it
also
enhanced
treatment
of
voltage-gated
calcium
channel
modulator
augment
presynaptic
release.
These
findings
highlight
importance
neuronal
types
activity
for
CNS
injuries.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 17, 2025
Rebuilding
functional
neuronal
circuits
after
injury
in
the
adult
central
nervous
system
(CNS)
is
unachievable
for
many
vertebrates.
In
pro-regenerative
models,
it
unclear
how
regeneration
and
re-wiring
achieved
CNS
over
long
distances.
The
size
opacity
of
vertebrate
brain
makes
difficult
to
study
axon
topography
dynamic
cellular
interactions
during
long-distance
regeneration.
Here,
we
harnessed
properties
small
transparent
Danionella
cerebrum
longitudinal
vivo
imaging
retinal
ganglion
cell
regeneration,
correlating
events
with
recovery.
Our
results
suggest
that
some
axons
regenerate
along
tracts
degenerating
myelin
debris.
However,
re-innervation
different
suggesting
new
are
created
restore
vision.
D.
model
provides
a
unique
opportunity
visualize
experimentally
manipulate
spatial
temporal
intact
British Journal of Pharmacology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 9, 2024
Abstract
Background
and
Purpose
Retinal
ganglion
cells
(RGCs)
are
the
output
stage
of
retinal
information
processing,
via
their
axons
forming
optic
nerve
(ON).
ON
damage
leads
to
axonal
degeneration
death
RGCs,
results
in
vision
impairment.
Nerve
growth
factor
(NGF)
signalling
is
crucial
for
RGC
operations
visual
functions.
Here,
we
investigate
a
new
neuroprotective
mechanism
novel
therapeutic
candidate,
p75‐less,
TrkA‐biased
NGF
agonist
(hNGFp)
rat
degeneration,
comparison
with
wild
type
human
(hNGFwt).
Experimental
Approach
Both
neonate
adult
rats,
whether
subjected
or
not
lesion,
were
treated
intravitreal
injections
eye
drops
containing
either
hNGFp
hNGFwt.
Different
doses
drugs
administered
at
days
1,
4
7
after
injury
maximum
10
days,
when
immunofluorescence,
electrophysiology,
cellular
morphology,
cytokine
array
behaviour
studies
carried
out.
Pharmacokinetic
evaluation
was
performed
on
rabbits
ocular
drops.
Results
exerted
potent
neuroprotection
by
acting
microglia
cells,
outperformed
hNGFwt
rescuing
reducing
inflammatory
molecules.
Delayed
use
lesion
resulted
better
outcomes
compared
treatment
Moreover,
hNGFp‐based
less
algogenic
than
measurements
revealed
that
biologically
relevant
quantities
found
rabbit
retina.
Conclusions
Implications
Our
data
point
as
cell
target
through
which
NGF‐induced
TrkA
exerts
RGC,
emphasizing
powerful
tackle
degeneration.
European Journal of Neuroscience,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 24, 2024
Abstract
Initial
symptoms
of
neurodegenerative
diseases
are
often
defined
by
the
loss
most
vulnerable
neural
populations
specific
to
each
disorder.
In
early
stages
Alzheimer's
disease,
circuits
in
temporal
lobe
exhibit
diminished
activity
prior
overt
degeneration.
It
remains
unclear
whether
these
functional
changes
contribute
regional
vulnerability
or
simply
a
consequence
pathology.
We
previously
found
that
entorhinal
neurons
cortex
undergo
cell
death
following
transient
suppression
electrical
activity,
suggesting
causal
role
for
disruption
neurodegeneration.
Here
we
demonstrate
arrest
this
circuit
stimulates
injury‐response
transcription
factor
c‐Jun.
Entorhinal
silencing
induces
transcriptional
consistent
with
c‐Jun
activation
share
characteristics
gene
signatures
other
neuronal
disease.
Despite
its
established
injury
response,
inhibiting
failed
ameliorate
degeneration
disruption.
Finally,
present
preliminary
evidence
integrated
stress
response
may
serve
as
an
alternative
hypothesis
what
drives
after
silencing.
Our
data
is
activated
but
decoupled
from
subsequent
