Brain,
Год журнала:
2020,
Номер
143(9), С. 2803 - 2817
Опубликована: Июнь 23, 2020
Accumulation
of
phosphorylated
tau
is
a
key
pathological
feature
Alzheimer's
disease.
Phosphorylated
accumulation
causes
synaptic
impairment,
neuronal
dysfunction
and
formation
neurofibrillary
tangles.
The
actions
are
mediated
by
surrounding
proteins;
however,
comprehensive
understanding
the
proteins
that
interacts
with
in
disease
surprisingly
limited.
Therefore,
aim
this
study
was
to
determine
interactome.
To
end,
we
used
two
complementary
proteomics
approaches:
(i)
quantitative
performed
on
tangles
microdissected
from
patients
advanced
disease;
(ii)
affinity
purification-mass
spectrometry
identify
which
these
specifically
bound
tau.
We
identified
542
This
included
abundant
detection
many
known
be
present
such
as
tau,
ubiquitin,
neurofilament
apolipoprotein
E.
Affinity
confirmed
75
interacted
PHF1-immunoreactive
Twenty-nine
have
been
previously
associated
therefore
validating
our
proteomic
approach.
More
importantly,
34
had
total
but
not
yet
linked
directly
(e.g.
protein
VAMP2,
vacuolar-ATPase
subunit
ATP6V0D1);
therefore,
provide
new
evidence
they
interact
In
addition,
also
12
novel
proteins,
physiologically
or
pathologically
RNA
binding
HNRNPA1).
Network
analysis
showed
interactome
enriched
involved
ubiquitination
pathway
phagosome
maturation.
Importantly,
were
able
pinpoint
specific
pathways
for
first
time,
providing
potential
pathogenic
mechanisms
can
explored
future
studies.
Combined,
results
reveal
drug
targets
treatment
tauopathies
insight
into
how
mediates
its
toxicity
Frontiers in Cellular Neuroscience,
Год журнала:
2015,
Номер
9
Опубликована: Май 26, 2015
Alzheimer’s
disease
(AD)
is
the
most
common
form
of
dementia
in
elderly,
and
affects
millions
people
worldwide.
As
number
AD
cases
continues
to
increase
both
developed
developing
countries,
finding
therapies
that
effectively
halt
or
reverse
progression
constitutes
a
major
research
public
health
challenge.
Since
identification
amyloid-b
peptide
(Ab)
as
component
amyloid
plaques
are
characteristically
found
brains,
effort
has
aimed
determine
whether
how
Ab
leads
memory
loss
cognitive
impairment.
A
large
body
evidence
accumulated
past
15
years
supports
pivotal
role
soluble
oligomers
(AbOs)
synapse
failure
neuronal
dysfunction
AD.
Nonetheless,
basic
questions,
including
exact
molecular
composition
synaptotoxic
oligomers,
identity
receptor(s)
which
they
bind,
signaling
pathways
ultimately
lead
failure,
remain
be
definitively
answered.
Here,
we
discuss
recent
advances
have
illuminated
our
understanding
chemical
nature
toxic
species
deleterious
impact
on
synapses,
culminated
proposal
an
oligomer
hypothesis
for
pathogenesis.
We
also
highlight
outstanding
questions
challenges
should
addressed
allow
translation
findings
into
effective
therapies.
Journal of Molecular Cell Biology,
Год журнала:
2014,
Номер
6(1), С. 64 - 74
Опубликована: Фев. 1, 2014
Wnts
comprise
a
large
family
of
proteins
that
have
shown
to
be
part
signaling
cascade
regulates
several
aspects
development
including
organogenesis,
midbrain
as
well
stem
cell
proliferation.
Wnt
pathway
plays
different
roles
in
the
neuronal
circuits
and
also
adult
brain,
where
it
synaptic
transmission
plasticity.
It
has
been
implicated
various
diseases
cancer
neurodegenerative
diseases,
reflecting
its
relevance
fundamental
biological
processes.
This
review
summarizes
progress
about
function
mature
nervous
system
with
focus
on
Alzheimer's
disease
(AD).
We
discuss
prospects
modulating
canonical
non-canonical
strategy
for
neuroprotection.
will
include
potential
to:
(i)
act
potent
regulators
hippocampal
synapses
impact
learning
memory;
(ii)
regulate
neurogenesis;
finally
(iii)
control
AD
pathogenesis.
Brain,
Год журнала:
2020,
Номер
143(9), С. 2803 - 2817
Опубликована: Июнь 23, 2020
Accumulation
of
phosphorylated
tau
is
a
key
pathological
feature
Alzheimer's
disease.
Phosphorylated
accumulation
causes
synaptic
impairment,
neuronal
dysfunction
and
formation
neurofibrillary
tangles.
The
actions
are
mediated
by
surrounding
proteins;
however,
comprehensive
understanding
the
proteins
that
interacts
with
in
disease
surprisingly
limited.
Therefore,
aim
this
study
was
to
determine
interactome.
To
end,
we
used
two
complementary
proteomics
approaches:
(i)
quantitative
performed
on
tangles
microdissected
from
patients
advanced
disease;
(ii)
affinity
purification-mass
spectrometry
identify
which
these
specifically
bound
tau.
We
identified
542
This
included
abundant
detection
many
known
be
present
such
as
tau,
ubiquitin,
neurofilament
apolipoprotein
E.
Affinity
confirmed
75
interacted
PHF1-immunoreactive
Twenty-nine
have
been
previously
associated
therefore
validating
our
proteomic
approach.
More
importantly,
34
had
total
but
not
yet
linked
directly
(e.g.
protein
VAMP2,
vacuolar-ATPase
subunit
ATP6V0D1);
therefore,
provide
new
evidence
they
interact
In
addition,
also
12
novel
proteins,
physiologically
or
pathologically
RNA
binding
HNRNPA1).
Network
analysis
showed
interactome
enriched
involved
ubiquitination
pathway
phagosome
maturation.
Importantly,
were
able
pinpoint
specific
pathways
for
first
time,
providing
potential
pathogenic
mechanisms
can
explored
future
studies.
Combined,
results
reveal
drug
targets
treatment
tauopathies
insight
into
how
mediates
its
toxicity
