The
cytosolic
proteins
synucleins
and
synapsins
are
thought
to
play
cooperative
roles
in
regulating
synaptic
vesicle
(SV)
recycling,
but
mechanistic
insight
is
lacking.
Here,
we
identify
the
synapsin
E-domain
as
an
essential
functional
binding-partner
of
α-synuclein
(α-syn).
Synapsin
allows
α-syn
functionality,
binds
α-syn,
necessary
sufficient
for
enabling
effects
at
synapses
cultured
mouse
hippocampal
neurons.
Together
with
previous
studies
implicating
clustering
SVs,
our
experiments
advocate
a
role
these
two
maintaining
physiologic
SV
clusters.
Cell Reports,
Journal Year:
2022,
Volume and Issue:
41(10), P. 111772 - 111772
Published: Dec. 1, 2022
Impaired
phosphodiesterase
(PDE)
function
and
mitochondrial
Ca2+
(i.e.,
[Ca2+]m)
lead
to
multiple
health
syndromes
by
an
unknown
pathway.
Here,
we
fluorescently
monitor
robust
[Ca2+]m
efflux
mediated
the
Na+/Ca2+
exchanger
NCLX
in
hippocampal
neurons
sequentially
evoked
caffeine
depolarization.
Surprisingly,
neuronal
depolarization-induced
transients
alone
fail
evoke
strong
wild-type
(WT)
neurons.
However,
pre-treatment
with
selective
PDE2
inhibitor
Bay
60-7550
effectively
rescues
similarly
caffeine.
Moreover,
acts
diminishing
cAMP,
thus
promoting
phosphorylation
at
its
PKA
site.
We
find
that
protection
of
against
excitotoxic
insults,
conferred
inhibition
WT
neurons,
is
dependent.
Finally,
administration
enhances
new
object
recognition
WT,
but
not
knockout
(KO),
mice.
Our
results
identify
a
link
between
PDE
signaling
may
provide
effective
therapy
for
cognitive
ischemic
syndromes.
Frontiers in Cellular Neuroscience,
Journal Year:
2022,
Volume and Issue:
16
Published: Aug. 5, 2022
Axonal
homeostasis
is
maintained
by
processes
that
include
cytoskeletal
regulation,
cargo
transport,
synaptic
activity,
ionic
balance,
and
energy
supply.
Several
of
these
involve
mitochondria
to
varying
degrees.
As
a
transportable
powerplant,
the
deliver
ATP
Ca
Journal of Biological Chemistry,
Journal Year:
2021,
Volume and Issue:
298(2), P. 101508 - 101508
Published: Dec. 20, 2021
The
mitochondrial
solute
carrier
family
8
sodium/calcium/lithium
exchanger,
member
B1
(NCLX)
is
an
important
mediator
of
calcium
extrusion
from
mitochondria.
In
this
study,
we
tested
the
hypothesis
that
physiological
expression
levels
NCLX
are
essential
for
maintaining
neuronal
resilience
in
face
excitotoxic
challenge.
Using
shRNA-mediated
approach,
showed
reduced
exacerbates
dysregulation,
membrane
potential
(ΔΨm)
breakdown,
and
reactive
oxygen
species
generation
during
stimulation
primary
hippocampal
cultures.
Moreover,
knockdown-which
affected
both
neurons
glia-resulted
not
only
enhanced
neurodegeneration
following
insult
but
also
astrocytic
cell
death
under
basal
conditions.
Our
data
revealed
synaptic
activity,
which
promotes
neuroprotective
signaling,
can
become
lethal
upon
depletion;
NCLX-targeted
shRNA
impaired
clearance
action
bursts,
was
associated
with
ΔΨm
breakdown
substantial
cultures
undergoing
activity.
Finally,
knockdown
within
cornu
ammonis
1
region
vivo
causes
astrodegeneration.
summary,
demonstrated
dysregulated
sensitizes
neuroglial
networks
to
stimuli
notably
renders
otherwise
activity
toxic.
These
findings
may
explain
emergence
astrodegeneration
patients
disorders
characterized
by
disrupted
or
function,
suggest
treatments
aimed
at
enhancing
restoring
function
prevent
central
nervous
system
damage
these
disease
states.
The
cytosolic
proteins
synucleins
and
synapsins
are
thought
to
play
cooperative
roles
in
regulating
synaptic
vesicle
(SV)
recycling,
but
mechanistic
insight
is
lacking.
Here,
we
identify
the
synapsin
E-domain
as
an
essential
functional
binding-partner
of
α-synuclein
(α-syn).
Synapsin
allows
α-syn
functionality,
binds
α-syn,
necessary
sufficient
for
enabling
effects
at
synapses
cultured
mouse
hippocampal
neurons.
Together
with
previous
studies
implicating
clustering
SVs,
our
experiments
advocate
a
role
these
two
maintaining
physiologic
SV
clusters.
