Acta Neuropathologica Communications,
Год журнала:
2021,
Номер
9(1)
Опубликована: Сен. 9, 2021
Abstract
In
this
review,
we
discuss
the
synaptic
aspects
of
Tau
pathology
occurring
during
Alzheimer’s
disease
(AD)
and
how
may
relate
to
memory
impairment,
a
major
hallmark
AD.
Whilst
clinical
diagnosis
AD
patients
is
loss
working
long-term
declarative
memory,
histological
presence
neurofibrillary
tangles
hyperphosphorylated
Amyloid-beta
plaques.
spreads
through
synaptically
connected
neurons
impair
function
preceding
formation
tangles,
loss,
axonal
retraction
cell
death.
Alongside
pathology,
recent
data
suggest
that
has
physiological
roles
in
pre-
or
post-
compartments.
Thus,
have
seen
shift
research
focus
from
as
microtubule-stabilising
protein
axons,
with
accelerating
spine
formation,
dendritic
elongation,
plasticity
coordinating
pathways.
We
collate
here
myriad
emerging
interactions
Tau,
current
evidence
contributes
Brain,
Год журнала:
2020,
Номер
144(1), С. 288 - 309
Опубликована: Окт. 7, 2020
Abstract
Extracellular
vesicles
are
highly
transmissible
and
play
critical
roles
in
the
propagation
of
tau
pathology,
although
underlying
mechanism
remains
elusive.
Here,
for
first
time,
we
comprehensively
characterized
physicochemical
structure
pathogenic
function
human
brain-derived
extracellular
isolated
from
Alzheimer’s
disease,
prodromal
non-demented
control
cases.
disease
were
significantly
enriched
epitope-specific
oligomers
comparison
to
or
as
determined
by
dot
blot
atomic
force
microscopy.
more
efficiently
internalized
murine
cortical
neurons,
well
efficient
transferring
misfolding
tau,
than
vitro.
Strikingly,
inoculation
containing
only
300
pg
into
outer
molecular
layer
dentate
gyrus
18-month-old
C57BL/6
mice
resulted
accumulation
abnormally
phosphorylated
throughout
hippocampus
4.5
months,
whereas
an
equal
amount
vesicles,
oligomers,
fibrils
same
donor
showed
little
pathology.
Furthermore,
induced
endogenous
both
oligomeric
sarkosyl-insoluble
forms
hippocampal
region.
Unexpectedly,
was
primarily
accumulated
glutamic
acid
decarboxylase
67
(GAD67)
GABAergic
interneurons
and,
a
lesser
extent,
glutamate
receptor
2/3-positive
excitatory
mossy
cells,
showing
preferential
vesicle-mediated
interneuronal
propagation.
Whole-cell
patch
clamp
recordings
CA1
pyramidal
cells
significant
reduction
amplitude
spontaneous
inhibitory
post-synaptic
currents.
This
accompanied
reductions
c-fos+
GAD67+
neurons
neuronal
puncta
surrounding
region,
confirming
reduced
transmission
this
Our
study
posits
novel
spread
via
their
subsequent
dysfunction.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(21), С. 12841 - 12841
Опубликована: Окт. 25, 2022
Alzheimer’s
disease
(AD)
is
the
leading
cause
of
dementia
in
elderly
people.
Amyloid
beta
(Aβ)
deposits
and
neurofibrillary
tangles
are
major
pathological
features
an
brain.
These
proteins
highly
expressed
nerve
cells
found
most
tissues.
Tau
primarily
provides
stabilization
to
microtubules
part
axons
dendrites.
However,
tau
a
state
becomes
hyperphosphorylated,
causing
dysfunction
synaptic
impairment
degeneration
neurons.
This
article
presents
summary
role
tau,
phosphorylated
(p-tau)
AD,
other
tauopathies.
Tauopathies,
including
Pick’s
disease,
frontotemporal
dementia,
corticobasal
degeneration,
argyrophilic
grain
progressive
supranuclear
palsy,
Huntington’s
result
misprocessing
accumulation
within
neuronal
glial
cells.
also
focuses
on
current
research
post-translational
modifications
genetics
pathology,
tauopathies
development
new
drugs
targeting
p-tau,
therapeutics
for
treating
possibly
preventing
Chemical Reviews,
Год журнала:
2021,
Номер
121(13), С. 8285 - 8307
Опубликована: Июнь 17, 2021
This
review
will
focus
on
the
process
of
amyloid-type
protein
aggregation.
Amyloid
fibrils
are
an
important
hallmark
misfolding
diseases
and
therefore
have
been
investigated
for
decades.
Only
recently,
however,
atomic
or
near-atomic
resolution
structures
elucidated
from
various
in
vitro
ex
vivo
obtained
fibrils.
In
parallel,
fibril
formation
has
studied
under
highly
artificial
but
comparatively
reproducible
conditions.
The
starts
with
a
summary
what
is
known
speculated
aggregation
experiments.
A
partially
hypothetic
selection
model
be
described
that
may
suitable
to
explain
why
amyloid
look
way
they
do,
particular,
at
least
all
so
far
reported
high
cryo-electron
microscopy
register,
cross-β-sheet
mostly
consist
two
protofilaments
twisted
around
each
other.
An
intrinsic
feature
prion-like
nature
assemblies.
Transferring
point
view
situation
not
straightforward,
hypothetic,
leaves
many
open
questions
need
addressed
future.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Апрель 14, 2021
Abstract
Disrupted
homeostasis
of
the
microtubule
binding
protein
tau
is
a
shared
feature
set
neurodegenerative
disorders
known
as
tauopathies.
Acetylation
soluble
an
early
pathological
event
in
neurodegeneration.
In
this
work,
we
find
that
large
fraction
neuronal
degraded
by
chaperone-mediated
autophagy
(CMA)
whereas,
upon
acetylation,
preferentially
macroautophagy
and
endosomal
microautophagy.
Rerouting
acetylated
to
these
other
autophagic
pathways
originates,
part,
from
inhibitory
effect
exerts
on
CMA
results
its
extracellular
release.
fact,
experimental
blockage
enhances
cell-to-cell
propagation
pathogenic
mouse
model
tauopathy.
Furthermore,
analysis
lysosomes
isolated
brains
patients
with
tauopathies
demonstrates
similar
molecular
mechanisms
leading
dysfunction.
This
study
reveals
failure
tauopathy
alters
could
contribute
aggravate
disease
progression.
Chemical Society Reviews,
Год журнала:
2021,
Номер
51(2), С. 513 - 565
Опубликована: Дек. 10, 2021
We
discuss
novel
approaches
for
embracing
and
reproducing
complexity
of
Tau
pathology
required
developing
disease-relevant
diagnostics
effective
therapies.
