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 Neurodegeneration,
Journal Year:
2014,
Volume and Issue:
9(1), P. 48 - 48
Published: Jan. 1, 2014
Alzheimer's
disease
(AD)
is
a
devastating
characterized
by
synaptic
and
neuronal
loss
in
the
elderly.
Compelling
evidence
suggests
that
soluble
amyloid-β
peptide
(Aβ)
oligomers
induce
AD.
Aβ-induced
dysfunction
dependent
on
overstimulation
of
N-methyl-D-aspartate
receptors
(NMDARs)
resulting
aberrant
activation
redox-mediated
events
as
well
elevation
cytoplasmic
Ca2+,
which
turn
triggers
downstream
pathways
involving
phospho-tau
(p-tau),
caspases,
Cdk5/dynamin-related
protein
1
(Drp1),
calcineurin/PP2B,
PP2A,
Gsk-3β,
Fyn,
cofilin,
CaMKII
causes
endocytosis
AMPA
(AMPARs)
NMDARs.
Dysfunction
these
leads
to
mitochondrial
dysfunction,
bioenergetic
compromise
consequent
loss,
impaired
long-term
potentiation
(LTP),
cognitive
decline.
Evidence
also
Aβ
may,
at
least
part,
mediate
causing
an
rise
extrasynaptic
glutamate
levels
inhibiting
uptake
or
triggering
release
from
glial
cells.
Consequent
NMDAR
(eNMDAR)
then
results
via
aforementioned
pathways.
Consistent
with
this
model
toxicity
can
be
partially
ameliorated
antagonists
(such
memantine
NitroMemantine).
PSD-95,
important
scaffolding
regulates
distribution
activity
both
NMDA
receptors,
functionally
disrupted
Aβ.
PSD-95
dysregulation
likely
intermediate
step
pathological
cascade
caused
In
summary,
complicated
process
multiple
pathways,
components
biological
events,
their
underlying
mechanisms,
albeit
yet
incompletely
understood,
may
offer
hope
for
new
therapeutic
avenues.
Journal of Molecular Cell Biology,
Journal Year:
2014,
Volume and Issue:
6(1), P. 64 - 74
Published: Feb. 1, 2014
Wnts
comprise
a
large
family
of
proteins
that
have
shown
to
be
part
signaling
cascade
regulates
several
aspects
development
including
organogenesis,
midbrain
as
well
stem
cell
proliferation.
Wnt
pathway
plays
different
roles
in
the
neuronal
circuits
and
also
adult
brain,
where
it
synaptic
transmission
plasticity.
It
has
been
implicated
various
diseases
cancer
neurodegenerative
diseases,
reflecting
its
relevance
fundamental
biological
processes.
This
review
summarizes
progress
about
function
mature
nervous
system
with
focus
on
Alzheimer's
disease
(AD).
We
discuss
prospects
modulating
canonical
non-canonical
strategy
for
neuroprotection.
will
include
potential
to:
(i)
act
potent
regulators
hippocampal
synapses
impact
learning
memory;
(ii)
regulate
neurogenesis;
finally
(iii)
control
AD
pathogenesis.
