bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 10, 2023
ABSTRACT
Membrane-bound
particles
in
plasma
are
composed
of
exosomes,
microvesicles,
and
apoptotic
bodies
represent
∼1-2%
the
total
protein
composition.
Proteomic
interrogation
this
subset
proteins
augments
representation
tissue-specific
proteins,
representing
a
“liquid
biopsy,”
while
enabling
detection
that
would
otherwise
be
beyond
dynamic
range
liquid
chromatography-tandem
mass
spectrometry
unfractionated
plasma.
We
have
developed
an
enrichment
strategy
(Mag-Net)
using
hyper-porous
strong-anion
exchange
magnetic
microparticles
to
sieve
membrane-bound
from
The
Mag-Net
method
is
robust,
reproducible,
inexpensive,
requires
<100
μL
input.
Coupled
quantitative
data-independent
analytical
strategy,
we
demonstrate
can
collect
results
for
>37,000
peptides
>4,000
with
high
precision.
Using
pipeline
on
small
cohort
patients
neurodegenerative
disease
healthy
age-matched
controls,
discovered
204
differentiate
(q-value
<
0.05)
Alzheimer’s
dementia
(ADD)
those
without
ADD.
Our
also
310
were
different
between
Parkinson’s
either
ADD
or
cognitively
normal
individuals.
machine
learning
able
distinguish
not
mean
ROC
AUC
=
0.98
±
0.06.
Cells,
Год журнала:
2022,
Номер
11(13), С. 2091 - 2091
Опубликована: Июнь 30, 2022
Neuroinflammation
is
a
hallmark
of
many
neurodegenerative
diseases
(NDs)
and
plays
fundamental
role
in
mediating
the
onset
progression
disease.
Microglia,
which
function
as
first-line
immune
guardians
central
nervous
system
(CNS),
are
drivers
neuroinflammation.
Numerous
human
postmortem
studies
vivo
imaging
analyses
have
shown
chronically
activated
microglia
patients
with
various
acute
chronic
neuropathological
diseases.
While
microglial
activation
common
feature
NDs,
exact
pathological
states
complex
often
contradictory.
However,
there
consensus
that
play
biphasic
conditions,
detrimental
protective
phenotypes,
overall
response
different
phenotypes
depends
on
nature
duration
inflammatory
insult,
well
stage
disease
development.
This
review
provides
comprehensive
overview
current
research
responses
health,
aging,
special
emphasis
heterogeneous
phenotypic
such
hemorrhagic
stroke
(HS),
Alzheimer's
(AD),
Parkinson's
(PD).
The
primary
focus
translational
preclinical
animal
models
bulk/single-cell
transcriptome
samples.
Additionally,
this
covers
key
receptors
signaling
pathways
potential
therapeutic
targets
to
regulate
during
aging
NDs.
age-,
sex-,
species-specific
differences
will
be
briefly
reviewed.
Journal of Extracellular Vesicles,
Год журнала:
2022,
Номер
11(1)
Опубликована: Янв. 1, 2022
Abstract
It
is
clear
from
Part
I
of
this
series
that
extracellular
vesicles
(EVs)
play
a
critical
role
in
maintaining
the
homeostasis
most,
if
not
all,
normal
physiological
systems.
However,
majority
our
knowledge
about
EV
signalling
has
come
studying
them
disease.
Indeed,
EVs
have
consistently
been
associated
with
propagating
disease
pathophysiology.
The
analysis
biofluids,
obtained
clinic,
an
essential
work
to
improve
understanding
their
interfere
for
therapeutic
gain,
more
fundamental
mechanisms
by
which
they
contribute
pathogenic
processes
required.
Only
discovering
how
populations
different
biofluids
change—size,
number,
and
physicochemical
composition—in
clinical
samples,
may
we
then
begin
unravel
functional
roles
translational
models
vitro
vivo,
can
feedback
clinic.
In
II
review
series,
pathology
will
be
discussed,
focus
on
vivo
evidence
potential
used
as
both
biomarkers
points
intervention.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Авг. 18, 2023
Abstract
Mitochondrial
quality
control
is
critical
for
cardiac
homeostasis
as
these
organelles
are
responsible
generating
most
of
the
energy
needed
to
sustain
contraction.
Dysfunctional
mitochondria
normally
degraded
via
intracellular
degradation
pathways
that
converge
on
lysosome.
Here,
we
identified
an
alternative
mechanism
eliminate
when
lysosomal
function
compromised.
We
show
inhibition
leads
increased
secretion
in
large
extracellular
vesicles
(EVs).
The
EVs
produced
multivesicular
bodies,
and
their
release
independent
autophagy.
Deletion
small
GTPase
Rab7
cells
or
adult
mouse
heart
containing
ubiquitinated
cargos,
including
intact
mitochondria.
secreted
captured
by
macrophages
without
activating
inflammation.
Hearts
from
aged
mice
Danon
disease
patients
have
levels
indicating
activation
vesicular
during
pathophysiology.
Overall,
findings
establish
eliminated
through
endosomal
pathway
inhibited.
Neuron,
Год журнала:
2023,
Номер
111(14), С. 2170 - 2183.e6
Опубликована: Май 15, 2023
In
Alzheimer's
disease,
fibrillar
tau
pathology
accumulates
and
spreads
through
the
brain
synapses
are
lost.
Evidence
from
mouse
models
indicates
that
trans-synaptically
pre-
to
postsynapses
oligomeric
is
synaptotoxic,
but
data
on
synaptic
in
human
scarce.
Here
we
used
sub-diffraction-limit
microscopy
study
accumulation
postmortem
temporal
occipital
cortices
of
control
donors.
Oligomeric
present
postsynaptic
terminals,
even
areas
without
abundant
deposition.
Furthermore,
there
a
higher
proportion
compared
with
phosphorylated
or
misfolded
found
at
terminals.
These
suggest
an
early
event
pathogenesis
may
progress
via
trans-synaptic
spread
disease.
Thus,
specifically
reducing
be
promising
therapeutic
strategy
for
The Journal of Experimental Medicine,
Год журнала:
2022,
Номер
220(1)
Опубликована: Сен. 9, 2022
Variants
in
the
triggering
receptor
expressed
on
myeloid
cells
2
(TREM2)
gene
are
associated
with
increased
risk
for
late-onset
AD.
Genetic
loss
of
or
decreased
TREM2
function
impairs
microglial
response
to
amyloid-β
(Aβ)
plaques,
resulting
more
diffuse
Aβ
plaques
and
peri-plaque
neuritic
dystrophy
AD-tau
seeding.
Thus,
microglia
at
a
critical
intersection
tau
pathologies
Since
genetically
decreasing
increases
Aβ-induced
seeding,
we
hypothesized
that
chronically
increasing
signaling
would
decrease
amyloid-induced
tau-seeding
spreading.
Using
mouse
model
amyloidosis
which
is
injected
into
brain
induce
Aβ-dependent
seeding/spreading,
found
chronic
administration
an
activating
antibody
activation
but
surprisingly
NP-tau
pathology
dystrophy,
without
altering
plaque
burden.
Our
data
suggest
sustained
through
does
not
result
strong
amyloid
removal
may
exacerbate
pathology,
have
important
clinical
implications.
Cells,
Год журнала:
2024,
Номер
13(2), С. 150 - 150
Опубликована: Янв. 12, 2024
The
blood-brain
barrier
(BBB)
is
a
fundamental
structure
that
protects
the
composition
of
brain
by
determining
which
ions,
metabolites,
and
nutrients
are
allowed
to
enter
from
blood
or
leave
it
towards
circulation.
BBB
structurally
composed
layer
capillary
endothelial
cells
(BCECs)
bound
each
other
through
tight
junctions
(TJs).
However,
its
development
as
well
maintenance
properties
controlled
contact
BCECs:
pericytes,
glial
cells,
even
neurons
themselves.
Astrocytes
seem,
in
particular,
have
very
important
role
controlling
most
BBB.
Here,
we
will
focus
on
these
latter
since
comprehension
their
roles
physiology
has
been
continuously
expanding,
including
ability
participate
neurotransmission
complex
functions
such
learning
memory.
Accordingly,
pathological
conditions
alter
astrocytic
can
BBB's
integrity,
thus
compromising
many
activities.
In
this
review,
also
refer
different
kinds
vitro
models
used
study
properties,
evidencing
modifications
under
conditions.
