Cellular and pathological functions of tau
Nature Reviews Molecular Cell Biology,
Год журнала:
2024,
Номер
25(11), С. 845 - 864
Опубликована: Июль 16, 2024
Язык: Английский
Inflammatory aspects of Alzheimer’s disease
Acta Neuropathologica,
Год журнала:
2024,
Номер
148(1)
Опубликована: Авг. 28, 2024
Язык: Английский
Clathrin mediated endocytosis in Alzheimer’s disease: cell type specific involvement in amyloid beta pathology
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Апрель 17, 2024
This
review
provides
a
comprehensive
examination
of
the
role
clathrin-mediated
endocytosis
(CME)
in
Alzheimer's
disease
(AD)
pathogenesis,
emphasizing
its
impact
across
various
cellular
contexts
beyond
neuronal
dysfunction.
In
neurons,
dysregulated
CME
contributes
to
synaptic
dysfunction,
amyloid
beta
(Aβ)
processing,
and
Tau
pathology,
highlighting
involvement
early
AD
pathogenesis.
Furthermore,
alterations
extend
non-neuronal
cell
types,
including
astrocytes
microglia,
which
play
crucial
roles
Aβ
clearance
neuroinflammation.
Dysregulated
these
cells
underscores
broader
implications
pathophysiology.
Despite
significant
progress,
further
research
is
needed
elucidate
precise
mechanisms
underlying
dysregulation
therapeutic
implications.
Overall,
understanding
complex
interplay
between
diverse
types
holds
promise
for
identifying
novel
targets
interventions.
Язык: Английский
Extracellular PHF-tau modulates astrocyte mitochondrial dynamics and mediates neuronal connectivity
Translational Neurodegeneration,
Год журнала:
2025,
Номер
14(1)
Опубликована: Март 24, 2025
Abstract
Background
Tau
is
an
intracellular
protein
that
plays
a
crucial
role
in
stabilizing
microtubules.
However,
it
can
aggregate
into
various
forms
under
pathological
conditions
and
be
secreted
the
brain
parenchyma.
While
consequences
of
tau
aggregation
within
neurons
have
been
extensively
studied,
effects
extracellular
paired
helical
filaments
(ePHF-tau)
on
astrocytes
are
still
poorly
understood.
Methods
This
study
examined
effect
human
ePHF-tau
(2N4R)
primary
cultures
rat
neuroglia,
focusing
changes
neurites
or
synapses
by
microscopy
analysis
synaptosome
mitochondria
proteomic
profiles
after
treatment.
In
addition,
we
monitored
behavior
separately
over
three
days
using
high-speed
imaging
high-throughput
acquisition
analysis.
Results
was
efficiently
cleared
two
3D
neuron-astrocyte
co-culture
model.
Treatment
with
led
to
rapid
increase
synaptic
vesicle
production
active
zones,
suggesting
potential
excitotoxic
response.
Proteomic
analyses
synaptosomal
mitochondrial
fractions
revealed
distinct
stress
adaptations:
exhibited
elevated
biogenesis
turnover,
whereas
neuronal
displayed
only
minor
oxidative
modifications.
mixed
culture
model,
overexpression
1N4R
specifically
triggered
marked
biogenesis,
coinciding
enhanced
formation
dendrites.
Similarly,
astrocyte-specific
PGC1alpha
produced
comparable
pattern
production,
indicating
astrocytic
adaptation
may
significantly
influence
function.
Conclusions
These
findings
suggest
accumulation
PHF-tau
drives
which
regulation.
astrocyte-mediated
tauopathy
highlights
modulating
dynamics
response
stress,
opening
avenues
for
therapeutic
strategies
aimed
at
mechanisms
context
neurodegenerative
diseases.
Язык: Английский
Astrocyte–Neuron Interactions in Alzheimer’s Disease
Advances in neurobiology,
Год журнала:
2024,
Номер
unknown, С. 345 - 382
Опубликована: Янв. 1, 2024
Язык: Английский
Neuroinflammatory Biomarkers in Alzheimer’s Disease: From Pathophysiology to Clinical Implications
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(22), С. 11941 - 11941
Опубликована: Ноя. 6, 2024
The
identification
of
neuroinflammation
as
a
critical
factor
in
Alzheimer's
disease
(AD)
has
expanded
the
focus
research
beyond
amyloid-β
and
tau
pathology.
neuroinflammatory
fluid
biomarkers
GFAP,
sTREM2,
YKL-40
have
gained
attention
for
their
potential
early
detection
monitoring
progression.
Plasma
GFAP
demonstrated
promise
predicting
conversion
from
mild
cognitive
impairment
to
AD
dementia,
while
sTREM2
highlights
microglial
activation,
although
there
are
conflicting
results
regarding
its
dynamics
pathogenesis.
Advanced
imaging
techniques,
such
PET
tracers
targeting
TSPO
MAO-B,
also
been
developed
visualize
glial
activation
vivo,
offering
spatial
temporal
insights
into
processes.
However,
clinical
implementation
these
faces
challenges
due
lack
specificity,
many
them
can
be
elevated
other
conditions.
Therapeutic
strategies
emerging,
with
TREM2-targeting
therapies
antidiabetic
drugs
like
GLP-1
receptor
agonists
showing
modulating
activity.
Nevertheless,
complexity
neuroinflammation,
which
encompasses
both
protective
harmful
responses,
necessitates
further
fully
unravel
role
optimize
therapeutic
approaches
AD.
Язык: Английский
Oligodendrocyte Dysfunction in Tauopathy: A Less Explored Area in Tau-Mediated Neurodegeneration
Cells,
Год журнала:
2024,
Номер
13(13), С. 1112 - 1112
Опубликована: Июнь 27, 2024
Aggregation
of
the
microtubule-associated
protein
tau
(MAPT)
is
hallmark
pathology
in
a
spectrum
neurodegenerative
disorders
collectively
called
tauopathies.
Physiologically,
an
inherent
neuronal
that
plays
important
role
assembly
microtubules
and
axonal
transport.
However,
disease-associated
mutations
this
reduce
its
binding
to
microtubule
components
promote
self-aggregation,
leading
formation
tangles
neurons.
Tau
also
expressed
oligodendrocytes,
where
it
has
significant
developmental
roles
oligodendrocyte
maturation
myelin
synthesis.
Oligodendrocyte-specific
pathology,
form
fibrils
coiled
coils,
evident
major
tauopathies
including
progressive
supranuclear
palsy
(PSP),
corticobasal
degeneration
(CBD),
Pick's
disease
(PiD).
Multiple
animal
models
tauopathy
expressing
mutant
forms
MAPT
recapitulate
oligodendroglial
inclusions
with
potential
cause
degeneration/malfunction
oligodendrocytes
affecting
sheath.
Till
now,
mechanistic
studies
heavily
concentrated
on
elucidating
pathology.
Therefore,
more
investigations
are
warranted
comprehensively
address
tau-induced
pathologies
oligodendrocytes.
The
present
review
provides
current
knowledge
available
literature
about
intricate
relations
between
health
diseases.
Язык: Английский
Amyloid-β oligomers increase the binding and internalization of tau oligomers in human synapses
Acta Neuropathologica,
Год журнала:
2024,
Номер
149(1)
Опубликована: Дек. 17, 2024
In
Alzheimer's
disease
(AD),
the
propagation
and
spreading
of
CNS
tau
pathology
closely
correlates
with
cognitive
decline,
positioning
as
an
attractive
therapeutic
target.
Amyloid
beta
(Aβ)
has
been
strongly
implicated
in
driving
spread,
whereas
primary
tauopathies
such
age-related
tauopathy
(PART)—which
lack
Aβ
pathology—exhibit
limited
spread
minimal-to-no
decline.
Emerging
evidence
converges
on
a
trans-synaptic
mechanism
facilitated
by
transfer
misfolded
aggregates
(e.g.
soluble
oligomers).
However,
it
is
unclear
whether
oligomers
modulate
binding
internalization
human
synapses.
Our
translationally
focused
paradigms
utilize
post-mortem
brain
specimens
from
Control,
PART,
AD
patients.
Synaptosomes
isolated
temporal
cortex
all
three
groups
were
incubated
preformed
recombinant
tauO
(rtauO),
±
AβO
(rAβO),
oligomer
binding/internalization
was
quantified
via
flow
cytometry
following
proteinase
K
(PK)
digestion
surface-bound
oligomers.
TauO-synapse
interactions
visualized
using
EM
immunogold.
Brain-derived
(BDTO)
PART
PBS-soluble
hippocampal
fractions
co-immunoprecipitated
analyzed
mass
spectrometry
to
compare
synaptic
interactomes
secondary
tauopathies,
thereby
inferring
role
Aβ.
synaptosomes,
enriched
endogenous
pathology,
exhibited
increased
rtauO
compared
synaptosomes.
This
observation
mirrored
Control
where
rAβO
significantly
internalization.
PK
pre-treatment
abolished
this
effect,
implicating
membrane
proteins
AβO-mediated
While
both
BDTO
broadly
proteins,
differential
enrichment
endocytic
across
pre-
post-synaptic
compartments,
showed
no
significant
enrichment.
study
demonstrates
that
enhance
drive
its
through
proteins.
These
findings
offer
novel
mechanistic
insights
underlying
pathological
directly
within
synapses
emphasize
potential
targeting
Aβ-tau
interactions.
Язык: Английский
Properties of Alzheimers disease brain-derived tau aggregates define tau processing by human astrocytes.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 5, 2024
Summary
The
templated
misfolding
of
tau
proteins
accounts
for
pathology
spread
in
Alzheimer’s
disease
(AD).
Post-translational
modifications,
including
phosphorylation
at
specific
residues,
are
closely
linked
with
seeding
ability
and
clinical
progression.
Increasing
evidence
supports
a
contributing
role
astrocytes
spread.
This
study
demonstrates
that
aggregates
from
postmortem
AD
brain
internalized
processed
by
human
astrocytes.
Differences
the
efficiency
internalization,
clearance
and/or
were
noted,
which
may
reflect
molecular
properties
tau.
Notably,
we
observed
direct
relationship
between
alterations
handling
astrocyte
responses,
evident
transcriptomic
data.
Dysregulated
genes
include
several
previously
identified
as
upregulated
reactive
brain,
well
being
implicated
pathological
autophagy
other
pathways.
provides
new
insights
into
complex
interplay
diversity
responses
AD.
Язык: Английский