Molecular Brain,
Journal Year:
2021,
Volume and Issue:
14(1)
Published: July 27, 2021
Abstract
Accumulating
evidence
indicates
that
the
actin
regulator
cofilin
is
overactivated
in
Alzheimer’s
Disease
(AD),
but
whether
this
abnormality
contributes
to
synaptic
and
cognitive
impairments
AD
unclear.
In
addition,
brain
region
cell
types
involved
remain
unknown.
study,
we
specifically
manipulate
LIMK1,
key
protein
kinase
phosphorylates
inactivates
cofilin,
hippocampus
of
APP/PS1
transgenic
mice.
Using
local
injections
AAV
virus
containing
LIMK1
under
control
CaMKIIα
promoter,
show
expression
hippocampal
excitatory
neurons
increases
phosphorylation
(i.e.,
decreases
activity),
rescues
long-term
potentiation,
improves
social
memory
Our
results
suggest
deficits
LIMK1/cofilin
signaling
contribute
pathology
manipulations
activity
provide
a
potential
therapeutic
strategy
treat
AD.
Brain,
Journal Year:
2023,
Volume and Issue:
146(10), P. 4350 - 4365
Published: May 31, 2023
Alzheimer's
disease,
the
most
common
cause
of
dementia,
is
a
chronic
degenerative
disease
with
typical
pathological
features
extracellular
senile
plaques
and
intracellular
neurofibrillary
tangles
significant
decrease
in
density
neuronal
dendritic
spines.
Cdc42
member
small
G
protein
family
that
plays
an
important
role
regulating
synaptic
plasticity
regulated
by
Cdc42GAP,
which
switches
from
active
GTP-bound
to
inactive
GDP-bound
states
downstream
pathways
via
effector
proteins.
However,
few
studies
have
focused
on
progression
disease.
In
heterozygous
Cdc42GAP
mouse
model
exhibited
elevated
Cdc42-GTPase
activity
accompanied
increased
Cdc42-PAK1-cofilin
signalling,
we
found
impairments
cognitive
behaviours,
neuron
senescence,
loss
depolymerization
F-actin
phenotypes
including
phosphorylated
tau
(p-T231,
AT8),
along
soluble
insoluble
Aβ1-42
Aβ1-40,
are
consistent
mice.
Interestingly,
these
significantly
age.
Furthermore,
results
quantitative
phosphoproteomic
analysis
hippocampus
11-month-old
GAP
mice
suggested
deficiency
induces
accelerates
disease-like
through
activation
GSK-3β
dephosphorylation
at
Ser9,
Ser389
and/or
phosphorylation
Tyr216.
addition,
overexpression
dominant-negative
primary
hippocampal
cortical
neurons
reversed
hyperphosphorylation.
Importantly,
signalling
pathway,
Aβ1-42,
Aβ1-40
were
sections
patients
compared
those
healthy
controls.
Together,
data
indicated
involved
such
as
deficits,
spine
loss,
AT8)
possibly
GSK-3β,
Thus,
provide
first
evidence
phenotypes,
may
new
targets
for
treatment.
eNeuro,
Journal Year:
2024,
Volume and Issue:
11(3), P. ENEURO.0497 - 23.2024
Published: Feb. 21, 2024
Synaptic
plasticity
is
important
for
learning
and
memory
formation;
it
describes
the
strengthening
or
weakening
of
connections
between
synapses.
The
postsynaptic
part
excitatory
synapses
resides
in
dendritic
spines,
which
are
small
protrusions
on
dendrites.
One
key
features
synaptic
its
correlation
with
size
these
spines.
A
long-lasting
strength
increase
[long-term
potentiation
(LTP)]
only
possible
through
reconfiguration
actin
spine
cytoskeleton.
Here,
we
develop
an
experimentally
informed
three-dimensional
computational
model
a
moving
boundary
framework
to
investigate
this
reconfiguration.
Our
reactions
actin-binding
proteins
leading
cytoskeleton
remodeling
their
effect
membrane
shape
examine
enlargement
upon
LTP.
Moreover,
find
that
incorporation
perisynaptic
elements
enhances
LTP,
exhibiting
importance
accounting
when
studying
structural
shows
adaptation
repeated
stimuli
resulting
from
interactions
mechanical
forces.
The FASEB Journal,
Journal Year:
2023,
Volume and Issue:
37(5)
Published: March 31, 2023
Abstract
Associative
learning
and
memory
are
fundamental
behavioral
processes
through
which
organisms
adapt
to
complex
environments.
involves
long‐lasting
changes
in
synaptic
plasticity.
Dendritic
spines
tiny
protrusions
from
the
dendritic
shaft
of
principal
neurons,
providing
structural
basis
for
plasticity
brain
networks
response
external
stimuli.
Mounting
evidence
indicates
that
spine
dynamics
crucial
different
associative
phases,
including
acquisition,
consolidation,
reconsolidation.
Causally
bridging
is
still
limited
by
suitable
tools
measure
control
vivo
under
behaviorally
relevant
conditions.
Here,
we
review
data
remodeling
during
processing
outline
open
questions.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 3, 2025
In
addition
to
regulating
the
actin
cytoskeleton,
Cofilin
also
senses
and
responds
environmental
stress.
can
promote
cell
survival
or
death
depending
on
context.
Yet,
many
aspects
of
Cofilin's
role
in
need
clarification.
Here,
we
show
that
exposing
early
Oxford University Press eBooks,
Journal Year:
2025,
Volume and Issue:
unknown, P. 405 - 500
Published: Jan. 1, 2025
Abstract
This
chapter
provides
an
overview
of
activity-dependent
synaptic
plasticity
in
the
hippocampus.
It
outlines
basic
properties
long-term
potentiation
(LTP)
and
depression
(LTD)
pathways
that
form
core
hippocampal
trisynaptic
circuit,
notably
Schaffer
collateral/commissural
(SCC)
pathway
connecting
CA3
to
CA1
pyramidal
cells.
Other
significant
include
projections
from
medial
later
entorhinal
cortex
(EC)
distal
dendrites
principal
cells
all
subfields
mossy
fiber
projection
dendate
granule
The
then
delves
into
physiological
cell
biological
mechanisms
its
contribution
hippocampus-dependent
memory,
including
relationship
engrams.
Another
major
focus
is
role
dysregulated
synaptopathies,
with
a
particular
emphasis
on
neurodevelopmental,
psychiatric
neurodegenerative
brain
disorders.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 6, 2025
Abstract
JNKs
mediate
neuronal
damage
in
neurodegenerative
disease
and
inhibitors
of
JNK1
have
shown
anxiolytic
anti-depressive
effects
mice.
Here,
we
analyze
the
phosphoproteomes
hippocampus
nucleus
accumbens
from
DJNKI-1
(JNK
inhibitor)-infused
We
correlate
phospho-site
changes
with
anxiety-like
behaviours
elevated
plus
maze
light-dark
test
identify
unique
responder
Among
regulated
phosphosites,
several
lie
within
GSK3
motifs
are
exclusively
down-regulated.
Consistent
this,
GSK3β
is
inhibited
AKT
activated.
Importantly,
detect
multilevel
regulation
glucose
metabolism
enzymes
including
increased
PDPK1-S241
phosphorylation,
a
5-fold
increase
pyruvate
dehydrogenase
(PDHA1)-S-293
signifying
its
inhibition.
This
suggests
that
JNK
inhibitor
drives
metabolic
transformation
to
Warburg
response.
range
identified
synaptic
cytoskeletal
protein
phosphosite
discussed
context
JNK-regulated
anxiety
responses.
The
annotated
hippocampal
described
here
will
support
mechanistic
understanding
pathway
for
future
studies
brain
disorders.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(9), P. 4094 - 4094
Published: April 25, 2025
ADF/cofilins
form
a
family
of
small,
widely
expressed
actin-binding
proteins,
regulating
actin
dynamics
in
various
cellular
and
physiological
processes
all
eukaryotes,
from
yeasts
to
animals.
Changes
the
expression
ADF/cofilin
proteins
have
been
demonstrated
under
pathological
conditions.
The
well-established
role
cofilin
migration,
invasion,
epithelial-mesenchymal
transition,
apoptosis,
resistance
radiotherapy
chemotherapy,
immune
escape,
transcriptional
dysregulation
malignant
tumors
is
primarily
attributed
its
actin-modifying
activity.
Moreover,
drugs
targeting
this
function
developed
for
cancer
treatment.
However,
multilevel
regulation,
highly
diverse
effects
across
conditions,
conflicting
data
on
functional
consequences
altered
prompted
us
explore
additional
roles
cofilin-beyond
modulation-particularly
involvement
lipid
metabolism
mitochondrial
homeostasis.
Here,
we
review
recent
pathologies,
account
mutations
post-translational
modifications
these
their
consequences,
dwell
K63-type
ubiquitination
homeostasis,
more
specifically,
process
division
or
mitofission,
point
out
research,
describe
prospects
future
studies
functions.
Frontiers in Neuroscience,
Journal Year:
2023,
Volume and Issue:
17
Published: March 2, 2023
Although
the
identification
of
numerous
genes
involved
in
neurodevelopmental
disorders
(NDDs)
has
reshaped
our
understanding
their
etiology,
there
are
still
major
obstacles
way
developing
therapeutic
solutions
for
intellectual
disability
(ID)
and
other
NDDs.
These
include
extensive
clinical
genetic
heterogeneity,
rarity
recurrent
pathogenic
variants,
comorbidity
with
psychiatric
traits.
Moreover,
a
large
intragenic
mutational
landscape
is
at
play
some
NDDs,
leading
to
broad
range
symptoms.
Such
diversity
symptoms
due
different
effects
DNA
variations
have
on
protein
functions
impacts
downstream
biological
processes.
The
type
functional
alterations,
such
as
loss
or
gain
function,
interference
signaling
pathways,
yet
be
correlated
most
genes.
This
review
aims
discussing
current
how
molecular
changes
group
I
p21-activated
kinases
(
PAK1
,
2
3
),
which
essential
actors
brain
development
function;
contribute
spectrum
Identifying
differences
PAK
structure,
regulation
spatio-temporal
expression
may
help
specific
each
.
Deciphering
variation
affects
these
parameters
will
uncover
mechanisms
underlying
mutation
pathogenicity.
prerequisite
personalized
approaches.