Current Opinion in Neurobiology,
Journal Year:
2018,
Volume and Issue:
51, P. 60 - 69
Published: March 12, 2018
Recent
years
have
seen
cytoskeleton
dynamics
emerging
as
a
key
player
in
axon
regeneration.
The
cytoskeleton,
particular
microtubules
and
actin,
ensures
the
growth
of
neuronal
processes
maintains
singular,
highly
polarized
shape
neurons.
Following
injury,
adult
central
axons
are
tipped
by
dystrophic
structure,
retraction
bulb,
which
prevents
their
Abnormal
responsible
for
formation
this
growth-incompetent
structure
but
pharmacologically
modulating
injured
can
transform
into
growth-competent
cone.
also
drives
migration
scar-forming
cells
after
an
injury.
Targeting
its
modifies
composition
inhibitory
environment
formed
scar
tissue
renders
it
more
permissive
regenerating
axons.
Hence,
represent
appealing
target
to
promote
As
some
cytoskeleton-targeting
drugs
used
clinics
other
purposes,
they
hold
promise
be
basis
regenerative
therapy
spinal
cord
The Journal of Physiology,
Journal Year:
2016,
Volume and Issue:
594(13), P. 3521 - 3531
Published: Feb. 10, 2016
Abstract
Nerve
injury
triggers
the
conversion
of
myelin
and
non‐myelin
(Remak)
Schwann
cells
to
a
cell
phenotype
specialized
promote
repair.
Distal
damage,
these
repair
provide
necessary
signals
spatial
cues
for
survival
injured
neurons,
axonal
regeneration
target
reinnervation.
The
involves
de‐differentiation
together
with
alternative
differentiation,
or
activation,
combination
that
is
typical
type
conversions
often
referred
as
(direct
lineage)
reprogramming.
Thus,
injury‐induced
reprogramming
down‐regulation
genes
combined
activation
set
repair‐supportive
features,
including
up‐regulation
trophic
factors,
elevation
cytokines
part
innate
immune
response,
clearance
by
autophagy
in
macrophage
recruitment,
formation
tracks,
Bungner's
bands,
directing
axons
their
targets.
This
programme
controlled
transcriptionally
mechanisms
involving
transcription
factor
c‐Jun,
which
rapidly
up‐regulated
after
injury.
In
absence
damage
results
dysfunctional
cell,
neuronal
death
failure
functional
recovery.
although
not
required
development,
therefore
central
future,
signalling
specifies
this
requires
further
analysis
so
pharmacological
tools
boost
maintain
can
be
developed.
image
Nature Communications,
Journal Year:
2019,
Volume and Issue:
10(1)
Published: Aug. 28, 2019
Abstract
Traumatic
spinal
cord
injury
results
in
severe
and
irreversible
loss
of
function.
The
triggers
a
complex
cascade
inflammatory
pathological
processes,
culminating
formation
scar.
While
traditionally
referred
to
as
glial
scar,
the
scar
fact
comprises
multiple
cellular
extracellular
components.
This
multidimensional
nature
should
be
considered
when
aiming
understand
role
scarring
limiting
tissue
repair
recovery.
In
this
Review
we
discuss
recent
advances
understanding
composition
phenotypic
characteristics
oversimplification
defining
binary
terms
good
or
bad,
development
therapeutic
approaches
target
components
enable
improved
functional
outcome
after
injury.
Journal of Clinical Investigation,
Journal Year:
2017,
Volume and Issue:
127(9), P. 3259 - 3270
Published: July 23, 2017
Spinal
cord
injury
(SCI)
lesions
present
diverse
challenges
for
repair
strategies.
Anatomically
complete
injuries
require
restoration
of
neural
connectivity
across
lesions.
incomplete
may
benefit
from
augmentation
spontaneous
circuit
reorganization.
Here,
we
review
SCI
cell
biology,
which
varies
considerably
three
different
lesion-related
tissue
compartments:
(a)
non-neural
lesion
core,
(b)
astrocyte
scar
border,
and
(c)
surrounding
spared
but
reactive
tissue.
After
SCI,
axon
growth
reorganization
are
determined
by
neuron-cell-autonomous
mechanisms
interactions
among
neurons,
glia,
immune
other
cells.
These
shaped
both
the
presence
absence
growth-modulating
molecules,
vary
markedly
in
compartments.
The
emerging
understanding
how
biology
differs
compartments
is
fundamental
to
developing
rationally
targeted
Science,
Journal Year:
2015,
Volume and Issue:
348(6232), P. 347 - 352
Published: March 13, 2015
After
central
nervous
system
(CNS)
injury,
inhibitory
factors
in
the
lesion
scar
and
poor
axon
growth
potential
prevent
regeneration.
Microtubule
stabilization
reduces
scarring
promotes
growth.
However,
cellular
mechanisms
of
this
dual
effect
remain
unclear.
Here,
delayed
systemic
administration
a
blood-brain
barrier-permeable
microtubule-stabilizing
drug,
epothilone
B
(epoB),
decreased
after
rodent
spinal
cord
injury
(SCI)
by
abrogating
polarization
directed
migration
scar-forming
fibroblasts.
Conversely,
reactivated
neuronal
inducing
concerted
microtubule
polymerization
into
tip,
which
propelled
through
an
environment.
Together,
these
drug-elicited
effects
promoted
regeneration
improved
motor
function
SCI.
With
recent
clinical
approval,
epothilones
hold
promise
for
use
CNS
injury.
Proceedings of the National Academy of Sciences,
Journal Year:
2013,
Volume and Issue:
110(10), P. 4039 - 4044
Published: Feb. 19, 2013
The
cell
intrinsic
factors
that
determine
whether
a
neuron
regenerates
or
undergoes
apoptosis
in
response
to
axonal
injury
are
not
well
defined.
Here
we
show
the
mixed-lineage
dual
leucine
zipper
kinase
(DLK)
is
an
essential
upstream
mediator
of
both
these
divergent
outcomes
same
type.
Optic
nerve
crush
leads
rapid
elevation
DLK
protein,
first
axons
retinal
ganglion
cells
(RGCs)
and
then
their
bodies.
required
for
majority
gene
expression
changes
RGCs
initiated
by
injury,
including
induction
proapoptotic
regeneration-associated
genes.
Deletion
retina
results
robust
sustained
protection
from
degeneration
after
optic
injury.
Despite
this
improved
survival,
number
regrow
beyond
site
substantially
reduced,
even
when
tumor
suppressor
phosphatase
tensin
homolog
(PTEN)
deleted
enhance
growth
potential.
These
findings
demonstrate
seemingly
contradictory
responses
mechanistically
coupled
through
DLK-based
damage
detection
mechanism.
