Aging Cell,
Journal Year:
2020,
Volume and Issue:
19(3)
Published: Feb. 12, 2020
Abstract
A
common
hallmark
of
age‐dependent
neurodegenerative
diseases
is
an
impairment
adult
neurogenesis.
Wingless‐type
mouse
mammary
tumor
virus
integration
site
(Wnt)/β‐catenin
(WβC)
signalling
a
vital
pathway
for
dopaminergic
(DAergic)
neurogenesis
and
essential
system
during
embryonic
development
aging,
the
most
critical
risk
factor
Parkinson's
disease
(PD).
To
date,
there
no
known
cause
or
cure
PD.
Here
we
focus
on
potential
to
reawaken
impaired
neurogenic
niches
rejuvenate
repair
aged
PD
brain.
Specifically,
highlight
WβC
‐
in
plasticity
subventricular
zone
(SVZ),
largest
germinal
region
mature
brain
innervated
by
nigrostriatal
DAergic
terminals,
mesencephalic
aqueduct‐periventricular
(Aq‐PVR)
Wnt‐sensitive
niche,
which
proximity
SNpc
harbors
neural
stem
progenitor
cells
(NSCs)
with
potential.
The
cytosolic
accumulation
β‐catenin,
enters
nucleus
associates
T
cell
factor/lymphoid
enhancer
binding
(TCF/LEF)
transcription
factors,
leading
Wnt
target
genes.
Here,
underscore
dynamic
interplay
between
innervation
astroglial‐derived
factors
regulating
WβC‐dependent
key
genes
orchestrating
NSC
proliferation,
survival,
migration
differentiation.
Aging,
inflammation
oxidative
stress
synergize
neurotoxin
exposure
“turning
off”
switch
via
down‐regulation
nuclear
erythroid‐2‐related
2/Wnt‐regulated
signalosome,
player
maintenance
antioxidant
self‐defense
mechanisms
homeostasis.
Harnessing
WβC‐signalling
can
thus
restore
neurogenesis,
microenvironment,
promote
neurorescue
regeneration.
Molecular Brain,
Journal Year:
2019,
Volume and Issue:
12(1)
Published: Dec. 1, 2019
Abstract
Alzheimer’s
disease
(AD)
is
an
aging-related
neurological
disorder
characterized
by
synaptic
loss
and
dementia.
Wnt/β-catenin
signaling
essential
signal
transduction
pathway
that
regulates
numerous
cellular
processes
including
cell
survival.
In
brain,
not
only
crucial
for
neuronal
survival
neurogenesis,
but
it
plays
important
roles
in
regulating
plasticity
blood-brain
barrier
integrity
function.
Moreover,
activation
of
inhibits
amyloid-β
production
tau
protein
hyperphosphorylation
the
brain.
Critically,
greatly
suppressed
AD
brain
via
multiple
pathogenic
mechanisms.
As
such,
restoring
represents
a
unique
opportunity
rational
design
novel
therapies.
