Journal of Neurochemistry,
Journal Year:
2021,
Volume and Issue:
157(6), P. 2128 - 2144
Published: Feb. 14, 2021
Neuronal
network
dysfunction
is
a
hallmark
of
Alzheimer's
disease
(AD).
However,
the
underlying
pathomechanisms
remain
unknown.
We
analyzed
hippocampal
micronetwork
in
transgenic
McGill-R-Thy1-APP
rats
(APPtg)
at
beginning
extracellular
amyloid
beta
(Aβ)
deposition.
established
two-photon
Ca2+
-imaging
vivo
hippocampus
and
found
hyperactivity
CA1
neurons.
Patch-clamp
recordings
brain
slices
vitro
revealed
increased
neuronal
input
resistance
prolonged
action
potential
width
pyramidal
did
neither
observe
changes
synaptic
inhibition,
nor
excitation.
Our
data
support
view
that
intrinsic
excitability
neurons
may
precede
inhibitory
an
early
stage
Aβ-deposition
progression.
Abstract
Glycogen
synthase
kinase‐3
(GSK3),
consisting
of
GSK3α
and
GSK3β
subtypes,
is
a
complex
protein
kinase
that
regulates
numerous
substrates.
Research
has
observed
increased
GSK3
expression
in
the
brains
Alzheimer's
disease
(AD)
patients
models.
AD
neurodegenerative
disorder
with
diverse
pathogenesis
notable
cognitive
impairments,
characterized
by
Aβ
aggregation
excessive
tau
phosphorylation.
This
article
provides
an
overview
GSK3's
structure
regulation,
extensively
analyzing
its
relationship
factors.
overactivation
disrupts
neural
growth,
development,
function.
It
directly
promotes
phosphorylation,
amyloid
precursor
(APP)
cleavage,
leading
to
formation,
or
indirectly
triggers
neuroinflammation
oxidative
damage.
We
also
summarize
preclinical
research
highlighting
inhibition
activity
as
primary
therapeutic
approach
for
AD.
Finally,
pending
issues
like
lack
highly
specific
affinity‐driven
inhibitors,
are
raised
expected
be
addressed
future
research.
In
conclusion,
represents
target
treatment,
filled
hope,
challenges,
opportunities,
obstacles.
Journal of Clinical Investigation,
Journal Year:
2024,
Volume and Issue:
134(11)
Published: April 10, 2024
Tissue
regeneration
is
limited
in
several
organs
including
the
kidney,
contributing
to
high
prevalence
of
kidney
disease
globally.
However,
evolutionary
and
physiological
adaptive
responses
presence
renal
progenitor
cells
suggest
existing
remodeling
capacity.
This
study
uncovered
endogenous
tissue
mechanisms
that
were
activated
by
loss
body
fluid
salt
regulated
a
unique
niche
minority
cell
type
called
macula
densa
(MD).
Here
we
identified
neuronal
differentiation
features
MD
sense
local
systemic
environment,
secrete
angiogenic,
growth
extracellular
matrix
factors,
cytokines
chemokines,
control
resident
cells.
Serial
intravital
imaging,
nerve
factor
receptor
Wnt
mouse
models
transcriptome
analysis
revealed
cellular
molecular
these
functions.
Human
therapeutic
translation
studies
illustrated
clinical
potential
factors
CCN1
as
urinary
biomarker
target
chronic
disease.
The
concept
neuronally
differentiated
key
sensory
regulatory
responding
organ-specific
inputs
controls
progenitors
remodel
or
repair
tissues
may
be
applicable
other
diverse
regenerative
strategies.
International Journal of Molecular Sciences,
Journal Year:
2021,
Volume and Issue:
22(11), P. 5991 - 5991
Published: June 1, 2021
Amyloid-β
(Aβ)
1-40
and
1-42
peptides
are
key
mediators
of
synaptic
cognitive
dysfunction
in
Alzheimer's
disease
(AD).
Whereas
AD,
Aβ
is
found
to
act
as
a
pro-epileptogenic
factor
even
before
plaque
formation,
amyloid
pathology
has
been
detected
among
patients
with
epilepsy
increased
risk
developing
AD.
Among
aggregated
species,
soluble
oligomers
suggested
be
responsible
for
most
Aβ's
toxic
effects.
exert
extracellular
intracellular
toxicity
through
different
mechanisms,
including
interaction
membrane
receptors
the
formation
ion-permeable
channels
cellular
membranes.
These
damages,
linked
an
unbalance
between
excitatory
inhibitory
neurotransmission,
often
result
neuronal
hyperexcitability
neural
circuit
dysfunction,
which
turn
increase
deposition
facilitate
neurodegeneration,
resulting
Aβ-driven
vicious
loop.
In
this
review,
we
summarize
representative
literature
on
effects
that
oligomeric
induces
network
disorganization.
Journal of Neurochemistry,
Journal Year:
2021,
Volume and Issue:
157(6), P. 2128 - 2144
Published: Feb. 14, 2021
Neuronal
network
dysfunction
is
a
hallmark
of
Alzheimer's
disease
(AD).
However,
the
underlying
pathomechanisms
remain
unknown.
We
analyzed
hippocampal
micronetwork
in
transgenic
McGill-R-Thy1-APP
rats
(APPtg)
at
beginning
extracellular
amyloid
beta
(Aβ)
deposition.
established
two-photon
Ca2+
-imaging
vivo
hippocampus
and
found
hyperactivity
CA1
neurons.
Patch-clamp
recordings
brain
slices
vitro
revealed
increased
neuronal
input
resistance
prolonged
action
potential
width
pyramidal
did
neither
observe
changes
synaptic
inhibition,
nor
excitation.
Our
data
support
view
that
intrinsic
excitability
neurons
may
precede
inhibitory
an
early
stage
Aβ-deposition
progression.
