bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 8, 2025
Abstract
Tauopathies
are
neurodegenerative
diseases
that
pathologically
characterized
by
accumulation
of
misfolded
microtubule-associated
protein
tau
aggregates
in
the
brain.
Deubiquitination,
particularly
OTULIN,
a
unique
deubiquitinase
targeting
methionine-1
(M1)
linkages
from
linear
ubiquitin
chain
assembly
complex
(LUBAC)),
is
reportedly
associated
with
neurotoxic
proteins
several
diseases,
likely
including
tauopathies.
To
investigate
potential
roles
OTULIN
tauopathies,
we
analyzed
interactome
hippocampal
tissues
PS19
transgenic
(Tg)
mice
and
their
non-transgenic
(nTg)
littermate
controls
using
affinity
purification-mass
spectrometry
(AP-MS).
We
identified
705
800
enriched
Tg
nTg
samples,
respectively,
false
discovery
rate
(FDR)
<1%.
Of
these,
189
205
were
classified
as
probable
interactors
groups,
based
on
Significance
Analysis
INTeractome
(SAINT)
score
≥0.80
FDR
≤
5%.
A
total
84
group,
while
100
controls.
Functional
enrichment
analyses
revealed
OTULIN-interacting
group
pathways
related
to
spliceosome,
complement
coagulation
cascades,
ribosome,
whereas
those
immune
response
autophagy.
These
findings
suggest
may
play
critical
role
pathogenesis
tauopathy
this
mouse
model.
Highlights
analyzed.
ribosome.
implicated
ATP2A2
an
specifically
enhanced
mice.
Diseases,
Год журнала:
2024,
Номер
12(6), С. 110 - 110
Опубликована: Май 22, 2024
Early-onset
Alzheimer’s
disease
(EOAD),
defined
as
onset
before
65
years
of
age,
has
been
significantly
less
studied
than
the
“classic”
late-onset
form
(LOAD),
although
EOAD
often
presents
with
a
more
aggressive
course,
caused
by
variants
in
APP,
PSEN1,
and
PSEN2
genes.
significant
differences
from
LOAD,
including
encompassing
diverse
phenotypic
manifestations,
increased
genetic
predisposition,
variations
neuropathological
burden
distribution.
Phenotypically,
can
be
manifested
non-amnestic
variants,
sparing
hippocampi
tau
burden.
The
aim
this
article
is
to
review
different
bases,
risk
factors,
pathological
mechanisms,
diagnostic
approaches
between
LOAD
suggest
steps
further
our
understanding.
comprehension
monogenic
provide
valuable
insights
that
may
serve
roadmap
for
understanding
common
disease.
ABSTRACT
The
unfolded
protein
response
(UPR)
is
a
cell-autonomous
stress
aimed
at
restoring
homeostasis
due
to
the
accumulation
of
misfolded
proteins
in
endoplasmic
reticulum
(ER).
Viruses
often
hijack
host
cell
machinery,
leading
an
ER.
UPR
immediate
infected
this
stress,
aiming
restore
normal
function
by
halting
translation,
degrading
proteins,
and
activating
signaling
pathways
that
increase
production
molecular
chaperones.
cell-non-autonomous
involves
spreading
signals
from
initially
stressed
cells
neighboring
unstressed
lack
stressor.
Though
viruses
are
known
modulators
UPR,
recent
advancements
have
highlighted
plays
critical
role
elucidating
how
local
infections
cause
systemic
effects,
thereby
contributing
disease
symptoms
progression.
Additionally,
utilizing
devised
novel
strategies
establish
pro-viral
state,
promoting
virus
spread.
This
review
discusses
examples
broadened
understanding
progression
looking
beyond
non-autonomous
processes
mechanistic
details
inducers,
spreaders,
receivers
signals.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 8, 2025
Abstract
Tauopathies
are
neurodegenerative
diseases
that
pathologically
characterized
by
accumulation
of
misfolded
microtubule-associated
protein
tau
aggregates
in
the
brain.
Deubiquitination,
particularly
OTULIN,
a
unique
deubiquitinase
targeting
methionine-1
(M1)
linkages
from
linear
ubiquitin
chain
assembly
complex
(LUBAC)),
is
reportedly
associated
with
neurotoxic
proteins
several
diseases,
likely
including
tauopathies.
To
investigate
potential
roles
OTULIN
tauopathies,
we
analyzed
interactome
hippocampal
tissues
PS19
transgenic
(Tg)
mice
and
their
non-transgenic
(nTg)
littermate
controls
using
affinity
purification-mass
spectrometry
(AP-MS).
We
identified
705
800
enriched
Tg
nTg
samples,
respectively,
false
discovery
rate
(FDR)
<1%.
Of
these,
189
205
were
classified
as
probable
interactors
groups,
based
on
Significance
Analysis
INTeractome
(SAINT)
score
≥0.80
FDR
≤
5%.
A
total
84
group,
while
100
controls.
Functional
enrichment
analyses
revealed
OTULIN-interacting
group
pathways
related
to
spliceosome,
complement
coagulation
cascades,
ribosome,
whereas
those
immune
response
autophagy.
These
findings
suggest
may
play
critical
role
pathogenesis
tauopathy
this
mouse
model.
Highlights
analyzed.
ribosome.
implicated
ATP2A2
an
specifically
enhanced
mice.
