Alzheimer s & Dementia,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 28, 2024
Abstract
INTRODUCTION
Type
2
diabetes
increases
the
risk
of
Alzheimer's
disease
(AD)
dementia.
Insulin
signaling
dysfunction
exacerbates
tau
protein
phosphorylation,
a
hallmark
AD
pathology.
However,
comprehensive
impact
on
patterns
AD‐related
phosphoprotein
in
human
brain
remains
underexplored.
METHODS
We
performed
tandem
mass
tag–based
phosphoproteome
profiling
post
mortem
prefrontal
cortex
samples
from
191
deceased
older
adults
with
and
without
pathologic
AD.
RESULTS
Among
7874
quantified
phosphosites,
microtubule‐associated
(MAPT)
phosphorylated
at
T529
T534
(isoform
8
T212
T217)
were
more
abundant
showed
differential
associations
diabetes.
Network
analysis
co‐abundance
uncovered
synergistic
interactions
between
diabetes,
one
module
exhibiting
higher
MAPT
phosphorylation
(15
phosphosites)
another
displaying
lower
MAP1B
(22
phosphosites).
DISCUSSION
This
study
offers
phosphoproteomics
insights
into
shedding
light
mechanisms
that
can
inform
development
therapeutics
for
Highlights
The
dementia
is
increased
among
living
are
Microtubule‐associated
Phosphosite
networks
identified.
Pharmaceuticals,
Journal Year:
2024,
Volume and Issue:
17(10), P. 1313 - 1313
Published: Oct. 1, 2024
Traumatic
brain
injury
(TBI),
which
is
a
global
public
health
concern,
can
take
various
forms,
from
mild
concussions
to
blast
injuries,
and
each
damage
type
has
particular
mechanism
of
progression.
However,
TBI
condition
with
complex
pathophysiology
heterogenous
clinical
presentation,
makes
it
difficult
model
for
in
vitro
vivo
studies
obtain
relevant
results
that
easily
be
translated
the
setting.
Accordingly,
pharmacological
options
management
are
still
scarce.
Since
wide
spectrum
processes,
such
as
glucose
homeostasis,
food
intake,
body
temperature
regulation,
stress
response,
neuroprotection,
memory,
were
demonstrated
modulated
after
delivering
glucagon-like
peptide
1
(GLP-1)
or
GLP-1
receptor
agonists
into
brain,
we
aimed
speculate
on
their
potential
role
by
comprehensively
overviewing
preclinical
evidence.
Based
promising
data,
hold
extend
beyond
metabolic
disorders
address
unmet
needs
neuroprotection
recovery
TBI,
but
also
other
types
central
nervous
system
injuries
spinal
cord
cerebral
ischemia.
This
overview
lay
basis
tailoring
new
research
hypotheses
future
models
settings.
large-scale
trials
crucial
confirm
safety
efficacy
these
therapeutic
applications.
Alzheimer s & Dementia,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 28, 2024
Abstract
INTRODUCTION
Type
2
diabetes
increases
the
risk
of
Alzheimer's
disease
(AD)
dementia.
Insulin
signaling
dysfunction
exacerbates
tau
protein
phosphorylation,
a
hallmark
AD
pathology.
However,
comprehensive
impact
on
patterns
AD‐related
phosphoprotein
in
human
brain
remains
underexplored.
METHODS
We
performed
tandem
mass
tag–based
phosphoproteome
profiling
post
mortem
prefrontal
cortex
samples
from
191
deceased
older
adults
with
and
without
pathologic
AD.
RESULTS
Among
7874
quantified
phosphosites,
microtubule‐associated
(MAPT)
phosphorylated
at
T529
T534
(isoform
8
T212
T217)
were
more
abundant
showed
differential
associations
diabetes.
Network
analysis
co‐abundance
uncovered
synergistic
interactions
between
diabetes,
one
module
exhibiting
higher
MAPT
phosphorylation
(15
phosphosites)
another
displaying
lower
MAP1B
(22
phosphosites).
DISCUSSION
This
study
offers
phosphoproteomics
insights
into
shedding
light
mechanisms
that
can
inform
development
therapeutics
for
Highlights
The
dementia
is
increased
among
living
are
Microtubule‐associated
Phosphosite
networks
identified.
