Science,
Journal Year:
2008,
Volume and Issue:
321(5896), P. 1686 - 1689
Published: Sept. 18, 2008
The
neurodegeneration
observed
in
Alzheimer's
disease
has
been
associated
with
synaptic
dismantling
and
progressive
decrease
neuronal
activity.
We
tested
this
hypothesis
vivo
by
using
two-photon
Ca2+
imaging
a
mouse
model
of
disease.
Although
activity
was
seen
29%
layer
2/3
cortical
neurons,
21%
neurons
displayed
an
unexpected
increase
the
frequency
spontaneous
transients.
These
"hyperactive"
were
found
exclusively
near
plaques
amyloid
beta-depositing
mice.
hyperactivity
appeared
to
be
due
relative
inhibition.
Thus,
we
suggest
that
redistribution
drive
between
silent
hyperactive
rather
than
overall
activity,
provides
mechanism
for
disturbed
function
New England Journal of Medicine,
Journal Year:
2010,
Volume and Issue:
362(4), P. 329 - 344
Published: Jan. 27, 2010
This
review
of
Alzheimer's
disease
assembles
a
variety
findings
relevant
to
the
mechanism
and
ties
them
together
using
current
understanding
basis
loss
cognition:
accumulation
misfolded
proteins,
which
cause
oxidative
inflammatory
damage
brain
and,
ultimately,
synaptic
dysfunction.
Pharmacological Reviews,
Journal Year:
2010,
Volume and Issue:
62(3), P. 405 - 496
Published: Aug. 17, 2010
The
mammalian
ionotropic
glutamate
receptor
family
encodes
18
gene
products
that
coassemble
to
form
ligand-gated
ion
channels
containing
an
agonist
recognition
site,
a
transmembrane
permeation
pathway,
and
gating
elements
couple
agonist-induced
conformational
changes
the
opening
or
closing
of
pore.
Glutamate
receptors
mediate
fast
excitatory
synaptic
transmission
in
central
nervous
system
are
localized
on
neuronal
non-neuronal
cells.
These
regulate
broad
spectrum
processes
brain,
spinal
cord,
retina,
peripheral
system.
postulated
play
important
roles
numerous
neurological
diseases
have
attracted
intense
scrutiny.
description
structure,
including
its
elements,
reveals
complex
assembly
multiple
semiautonomous
extracellular
domains
linked
pore-forming
element
with
striking
resemblance
inverted
potassium
channel.
In
this
review
we
discuss
International
Union
Basic
Clinical
Pharmacology
nomenclature,
assembly,
accessory
subunits,
interacting
proteins,
expression
translation,
post-translational
modifications,
antagonist
pharmacology,
allosteric
modulation,
mechanisms
permeation,
normal
physiological
function,
as
well
potential
therapeutic
use
pharmacological
agents
acting
at
receptors.
Journal of Neurochemistry,
Journal Year:
2007,
Volume and Issue:
101(5), P. 1172 - 1184
Published: Jan. 4, 2007
Abstract
Converging
lines
of
evidence
suggest
that
progressive
accumulation
the
amyloid
β‐protein
(Aβ)
plays
a
central
role
in
genesis
Alzheimer’s
disease,
but
it
was
long
assumed
Aβ
had
to
be
assembled
into
extracellular
fibrils
exert
its
cytotoxic
effects.
Over
past
decade,
data
have
emerged
from
use
synthetic
peptides,
cell
culture
models,
β‐amyloid
precursor
protein
transgenic
mice
and
human
brain
pre‐fibrillar,
diffusible
assemblies
are
also
deleterious.
Although
precise
molecular
identity
these
soluble
toxins
remains
unsettled,
accumulating
suggests
forms
indeed
proximate
effectors
synapse
loss
neuronal
injury.
Here
we
review
recent
progress
understanding
oligomers
disease.
