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
synapse.
Together
with
previous
studies
implicating
clustering
SVs,
our
experiments
advocate
a
role
these
two
maintaining
physiologic
SV
clusters.
Cell Calcium,
Journal Year:
2023,
Volume and Issue:
111, P. 102719 - 102719
Published: March 21, 2023
The
mitochondrial
Permeability
Transition
Pore
(PTP)
can
be
defined
as
a
Ca2+
activated
mega-channel
involved
in
damage
and
cell
death,
making
its
inhibition
hallmark
for
therapeutic
purposes
many
PTP-related
paradigms.
Although
long-lasting
PTP
openings
have
been
widely
studied,
the
physiological
implications
of
transient
(also
called
"flickering"
behavior)
are
still
poorly
understood.
flickering
activity
was
suggested
to
play
role
regulation
ROS
homeostasis,
yet
this
hypothesis
did
not
reach
general
consensus.
This
state
affairs
might
arise
from
lack
unquestionable
experimental
evidence,
due
limitations
available
techniques
capturing
partial
understanding
molecular
identity.
In
review
we
will
focus
on
possible
physiology,
particular
release
pathway,
discussing
consequences
forced
inhibition.
We
also
consider
recent
existence
more
permeability
pathways
their
potential
involvement
physiology.
Science Advances,
Journal Year:
2022,
Volume and Issue:
8(11)
Published: March 18, 2022
Dysregulation
of
mitochondrial
Ca
2+
homeostasis
has
been
linked
to
neurodegenerative
diseases.
Mitochondrial
uptake
is
mediated
via
the
calcium
uniporter
complex
that
primarily
regulated
by
MICU1,
a
-sensing
gatekeeper.
Recently,
human
patients
with
MICU1
loss-of-function
mutations
were
diagnosed
neuromuscular
and
cognitive
impairments.
While
studies
in
patient-derived
cells
revealed
altered
signaling,
neuronal
pathogenesis
was
difficult
study.
To
fill
this
void,
we
created
neuron-specific
MICU1-KO
mouse
model.
These
animals
show
progressive,
abnormal
motor
phenotypes
likely
caused
degeneration
neurons
spinal
cord
cortex.
We
found
increased
susceptibility
overload-induced
excitotoxic
insults
cell
death
MICU1-deficient
cells,
which
can
be
blunted
inhibiting
permeability
transition
pore.
Thus,
our
study
identifies
as
causative
clinical
symptoms
highlights
potential
therapeutic
targets.
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.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging,
Journal Year:
2021,
Volume and Issue:
7(5), P. 498 - 509
Published: Nov. 17, 2021
The
association
between
maternal
immune
activation
(MIA)
during
pregnancy
and
risk
for
offspring
neuropsychiatric
disorders
has
been
increasingly
recognized
over
the
past
several
years.
Among
mechanistic
pathways
that
have
described
through
which
inflammation
may
affect
fetal
brain
development,
role
of
mitochondria
received
little
attention.
In
this
review,
as
a
potential
mediator
MIA
development
psychiatric
will
be
proposed.
As
basis
postulation,
convergent
evidence
is
presented
supporting
obligatory
in
mediators
initiators
inflammatory
processes,
mitochondrial
dysfunction
preclinical
exposure
models
human
neurodevelopmental
disorders.
Elucidating
MIA-induced
alterations
disease
not
only
provide
new
insight
into
pathophysiology
mental
health
their
origins
to
infection/immune
but
also
offer
therapeutic
targets.
Life Science Alliance,
Journal Year:
2022,
Volume and Issue:
5(10), P. e202201478 - e202201478
Published: June 17, 2022
Ion
fluxes
across
the
inner
mitochondrial
membrane
control
volume,
energy
production,
and
apoptosis.
TMBIM5,
a
highly
conserved
protein
with
homology
to
putative
pH-dependent
ion
channels,
is
involved
in
maintenance
of
cristae
architecture,
ATP
Here,
we
demonstrate
that
overexpressed
TMBIM5
can
mediate
calcium
uptake.
Under
steady-state
conditions,
loss
results
increased
potassium
reduced
proton
levels
matrix
caused
by
attenuated
exchange
these
ions.
To
identify
vivo
consequences
dysfunction,
generated
mice
carrying
mutation
channel
pore.
These
mutant
display
embryonic
or
perinatal
lethality
skeletal
myopathy
which
strongly
correlates
tissue-specific
disruption
early
opening
permeability
transition
pore,
uptake
capability,
swelling.
Our
an
essential
important
part
transport
system
machinery
particular
importance
for
development
muscle
function.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(19), P. 14450 - 14450
Published: Sept. 22, 2023
This
review
is
devoted
to
the
problems
of
common
features
linking
metabolic
disorders
and
type
2
diabetes
with
development
Alzheimer’s
disease.
The
pathogenesis
disease
closely
intersects
mechanisms
development,
an
important
risk
factor
for
both
pathologies
aging.
Common
pathological
include
factors
in
oxidative
stress,
neuroinflammation,
insulin
resistance,
amyloidosis,
as
well
impaired
mitochondrial
dysfunctions
increasing
cell
death.
currently
available
drugs
treatment
have
limited
therapeutic
efficacy.
It
note
that
used
treat
disease,
particular
acetylcholinesterase
inhibitors,
show
a
positive
potential
diabetes,
while
can
also
prevent
number
characteristic
A
promising
direction
search
strategy
may
be
creation
complex
multi-target
neuroprotective
affect
specific
targets
Essays in Biochemistry,
Journal Year:
2023,
Volume and Issue:
67(1), P. 63 - 75
Published: Jan. 13, 2023
Abstract
Astrocytes
are
a
heterogenous
population
of
macroglial
cells
spread
throughout
the
central
nervous
system
with
diverse
functions,
expression
signatures,
and
intricate
morphologies.
Their
subcellular
compartments
contain
distinct
range
mitochondria,
functional
microdomains
exhibiting
widespread
activities,
such
as
controlling
local
metabolism
Ca2+
signaling.
is
an
ion
utmost
importance,
both
physiologically
pathologically,
participates
in
critical
processes,
including
synaptic
plasticity,
neuron–astrocyte
integration,
excitotoxicity,
mitochondrial
physiology
metabolism.
The
handling
formed
by
uniporter
complex
(MCUc),
which
mediates
influx,
Na+/Ca2+
exchanger
(NCLX),
responsible
for
most
efflux,
well
additional
components,
permeability
transition
pore
(mtPTP).
Over
last
decades,
has
been
shown
to
be
key
brain
homeostasis,
acting
centrally
physiopathological
processes
astrogliosis,
astrocyte–neuron
activity
energy
control,
neurodegeneration.
In
this
review,
we
discuss
current
state
knowledge
regarding
molecular
composition,
highlighting
its
impact
on
astrocytic
homeostasis.
Food Frontiers,
Journal Year:
2023,
Volume and Issue:
4(2), P. 677 - 699
Published: Feb. 22, 2023
Abstract
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
with
an
insidious
onset
that
seriously
affects
human
health.
Plant‐derived
peptides
have
been
found
to
hinder
the
development
of
AD
pathologies,
which
excellent
candidate
for
preventing
AD.
However,
due
excessively
complicated
pathogenesis
and
fact
most
studies
on
activity
plant‐derived
are
single
not
deep
enough,
restricted
application
AD‐prevention
(PADPs).
This
review
summarized
currently
available
means
obtaining
PADPs,
in
vitro
vivo
validation
protocols,
molecular
pathways
structure–activity
relationship
between
activity,
some
perspectives
current
advanced
technologies.
paper
will
help
develop
foundation
production
exploitation
PADPs.
