Cell,
Год журнала:
2020,
Номер
183(6), С. 1699 - 1713.e13
Опубликована: Ноя. 13, 2020
To
elucidate
the
role
of
Tau
isoforms
and
post-translational
modification
(PTM)
stoichiometry
in
Alzheimer's
disease
(AD),
we
generated
a
high-resolution
quantitative
proteomics
map
95
PTMs
on
multiple
isolated
from
postmortem
human
tissue
49
AD
42
control
subjects.
Although
PTM
maps
reveal
heterogeneity
across
subjects,
subset
display
high
occupancy
frequency
for
AD,
suggesting
importance
disease.
Unsupervised
analyses
indicate
that
occur
an
ordered
manner,
leading
to
aggregation.
The
processive
addition
minimal
set
associated
with
seeding
activity
was
further
defined
by
analysis
size-fractionated
Tau.
summarize,
features
protein
critical
intervention
at
different
stages
are
identified,
including
enrichment
0N
4R
isoforms,
underrepresentation
C
terminus,
increase
negative
charge
proline-rich
region
(PRR),
decrease
positive
microtubule
binding
domain
(MBD).
European Journal of Neurology,
Год журнала:
2017,
Номер
25(1), С. 59 - 70
Опубликована: Сен. 5, 2017
Alzheimer's
disease,
the
commonest
cause
of
dementia,
is
a
growing
global
health
concern
with
huge
implications
for
individuals
and
society.
In
this
review,
current
understanding
epidemiology,
genetics,
pathology
pathogenesis
disease
outlined,
before
its
clinical
presentation
treatment
strategies
are
discussed.
Finally,
review
discusses
how
our
enhanced
Alzheimer
pathogenesis,
including
recognition
protracted
preclinical
phase,
informing
new
therapeutic
aim
moving
from
to
prevention.
Science,
Год журнала:
2016,
Номер
353(6301), С. 777 - 783
Опубликована: Авг. 18, 2016
Neurodegenerative
diseases
such
as
Alzheimer's
disease,
Parkinson's
amyotrophic
lateral
sclerosis,
and
frontotemporal
lobar
dementia
are
among
the
most
pressing
problems
of
developed
societies
with
aging
populations.
Neurons
carry
out
essential
functions
signal
transmission
network
integration
in
central
nervous
system
main
targets
neurodegenerative
disease.
In
this
Review,
I
address
how
neuron's
environment
also
contributes
to
neurodegeneration.
Maintaining
an
optimal
milieu
for
neuronal
function
rests
supportive
cells
termed
glia
blood-brain
barrier.
Accumulating
evidence
suggests
that
neurodegeneration
occurs
part
because
is
affected
during
disease
a
cascade
processes
collectively
neuroinflammation.
These
observations
indicate
therapies
targeting
glial
might
provide
benefit
those
afflicted
by
disorders.
Neurosurgery,
Год журнала:
2014,
Номер
75(Supplement 4), С. S24 - S33
Опубликована: Сен. 19, 2014
Since
the
original
descriptions
of
postconcussive
pathophysiology,
there
has
been
a
significant
increase
in
interest
and
ongoing
research
to
study
biological
underpinnings
concussion.
The
initial
ionic
flux
glutamate
release
result
energy
demands
period
metabolic
crisis
for
injured
brain.
These
physiological
perturbations
can
now
be
linked
clinical
characteristics
concussion,
including
migrainous
symptoms,
vulnerability
repeat
injury,
cognitive
impairment.
Furthermore,
advanced
neuroimaging
allows
window
monitor
postconcussion
pathophysiology
humans
noninvasively.
There
is
also
increasing
concern
about
risk
chronic
or
even
progressive
neurobehavioral
impairment
after
concussion/mild
traumatic
brain
injury.
Critical
studies
are
underway
better
link
acute
pathobiology
concussion
with
potential
mechanisms
cell
death,
dysfunction,
neurodegeneration.
This
"new
improved"
article
summarizes
translational
fashion
updates
what
known
neurometabolic
changes
concussive
new
connections
proposed
between
this
neurobiology
early
symptoms
as
well
cellular
processes
that
may
underlie
long-term
New England Journal of Medicine,
Год журнала:
2018,
Номер
378(4), С. 321 - 330
Опубликована: Янв. 25, 2018
Alzheimer's
disease
is
characterized
by
amyloid-beta
(Aβ)
plaques
and
neurofibrillary
tangles.
The
humanized
monoclonal
antibody
solanezumab
was
designed
to
increase
the
clearance
from
brain
of
soluble
Aβ,
peptides
that
may
lead
toxic
effects
in
synapses
precede
deposition
fibrillary
amyloid.
Science,
Год журнала:
2017,
Номер
358(6359), С. 116 - 119
Опубликована: Сен. 8, 2017
Amyloids
are
implicated
in
neurodegenerative
diseases.
Fibrillar
aggregates
of
the
amyloid-β
protein
(Aβ)
main
component
senile
plaques
found
brains
Alzheimer's
disease
patients.
We
present
structure
an
Aβ(1-42)
fibril
composed
two
intertwined
protofilaments
determined
by
cryo-electron
microscopy
(cryo-EM)
to
4.0-angstrom
resolution,
complemented
solid-state
nuclear
magnetic
resonance
experiments.
The
backbone
all
42
residues
and
nearly
side
chains
well
resolved
EM
density
map,
including
entire
N
terminus,
which
is
part
cross-β
resulting
overall
"LS"-shaped
topology
individual
subunits.
dimer
interface
protects
hydrophobic
C
termini
from
solvent.
characteristic
staggering
nonplanar
subunits
results
markedly
different
ends,
termed
"groove"
"ridge,"
leading
binding
pathways
on
both
has
implications
for
growth.
