Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients
Alzheimer s & Dementia,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 25, 2024
Abstract
BACKGROUND
Synaptic
and
extrasynaptic
distribution
of
N‐methyl‐D‐aspartate
receptors
(NMDARs)
has
not
been
addressed
in
the
brain
from
Alzheimer´s
disease
(AD)
subjects,
despite
their
contribution
to
neurodegeneration.
METHODS
We
have
developed
a
protocol
isolate
synaptic
membranes
controls
AD
frontal
cortex.
characterized
NMDAR
subunits
GluN2B,
GluN2A,
GluN1,
GluN3A,
as
well
post‐translational
modifications,
such
phosphorylation
glycosylation.
RESULTS
Lower
levels
GluN2B
GluN2A
were
found
fractions,
while
GluN1
significantly
higher;
GluN3A
remained
unaffected
AD.
also
identified
different
glycoforms
membranes.
Tyr1472
was
lower
fractions.
DISCUSSION
Reduction
subunits,
particularly
for
is
likely
contribute
transmission
failure
Additionally,
increment
could
favor
activation
excitotoxicity
Highlights
New
human
Low
High
Specific
GluN2A.
at
Язык: Английский
Mannose Promotes β‐Amyloid Pathology by Regulating BACE1 Glycosylation in Alzheimer's Disease
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Hyperglycemia
accelerates
Alzheimer's
disease
(AD)
progression,
yet
the
role
of
monosaccharides
remains
unclear.
Here,
it
is
demonstrated
that
mannose,
a
hexose,
closely
correlates
with
pathological
characteristics
AD,
as
confirmed
by
measuring
mannose
levels
in
brains
and
serum
AD
mice,
well
patients.
mice
are
given
intra-cerebroventricular
injection
(ICV)
or
drinking
water
to
investigate
effects
on
cognition
progression.
Chronic
overload
increases
β-amyloid
(Aβ)
burdens
exacerbates
cognitive
impairments,
which
reversed
mannose-free
diet
transporter
antagonists.
Mechanistically,
single-cell
RNA
sequencing
metabolomics
suggested
mannose-mediated
N-glycosylation
BACE1
Nicastrin
enhances
their
protein
stability,
promoting
Aβ
production.
Additionally,
reduced
intake
decreased
ultimately
lowering
production
mitigating
pathology.
this
results
highlight
high-dose
consumption
may
exacerbate
pathogenesis.
Restricting
dietary
have
therapeutic
benefits.
Язык: Английский
Recent Advances in Mass Spectrometry-Based Bottom-Up Proteomics
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Mass
spectrometry-based
proteomics
is
about
35
years
old,
and
recent
progress
appears
to
be
speeding
up
across
all
subfields.
In
this
review,
we
focus
on
advances
over
the
last
two
in
select
areas
within
bottom-up
proteomics,
including
approaches
high-throughput
experiments,
data
analysis
using
machine
learning,
drug
discovery,
glycoproteomics,
extracellular
vesicle
structural
proteomics.
Язык: Английский
Chemical Synthesis Reveals Pathogenic Role of N-Glycosylation in Microtubule-Associated Protein Tau
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 17, 2025
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
characterized
by
the
accumulation
of
tau
protein
aggregates.
In
this
study,
we
investigated
effects
N-glycosylation
on
tau,
focusing
its
impact
aggregation
and
phase
behavior.
We
chemically
prepared
homogeneous
glycoproteins
with
high-mannose
glycans
or
single
N-acetylglucosamine
at
confirmed
glycosylation
sites
in
K18
2N4R
tau.
Our
findings
reveal
that
significantly
alters
biophysical
properties
potentially
cellular
functions
Small
promote
liquid–liquid
separation
(LLPS),
while
larger
reduce
these
effects.
High
mannose
N410
enhance
phosphorylation
GSK3β,
suggesting
pathological
role
AD.
Functional
assays
demonstrate
does
not
microtubule
polymerization
dynamics
but
modulates
kinetics
morphology.
This
research
underscores
importance
pathology
opens
new
avenues
for
therapeutic
interventions
targeting
glycan
processing.
Язык: Английский
Aberrant glycosylation in schizophrenia: insights into pathophysiological mechanisms and therapeutic potentials
Yanchen Feng,
Lu Sun,
Xue Dang
и другие.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Сен. 2, 2024
Schizophrenia
(SCZ)
is
a
severe
neuropsychiatric
disorder
characterized
by
cognitive,
affective,
and
social
dysfunction,
resulting
in
hallucinations,
delusions,
emotional
blunting,
disordered
thinking.
In
recent
years,
proteomics
has
been
increasingly
influential
SCZ
research.
Glycosylation,
key
post-translational
modification,
can
alter
neuronal
stability
normal
signaling
the
nervous
system
affecting
protein
folding,
stability,
cellular
signaling.
Recent
research
evidence
suggests
that
abnormal
glycosylation
patterns
exist
different
brain
regions
autopsy
samples
from
patients,
there
are
significant
differences
various
modification
types
modifying
enzymes.
Therefore,
this
review
explores
mechanisms
of
aberrant
modifications
N-glycosylation,
O-glycosylation,
glycosyltransferases,
polysialic
acid
brains
emphasizing
their
roles
neurotransmitter
receptor
function,
synaptic
plasticity,
neural
adhesion.
Additionally,
effects
antipsychotic
drugs
on
processes
potential
for
glycosylation-targeted
therapies
discussed.
By
integrating
these
findings,
aims
to
provide
comprehensive
perspective
further
understand
role
pathophysiology
SCZ.
Язык: Английский
The tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs
Seminars in Immunology,
Год журнала:
2024,
Номер
76, С. 101913 - 101913
Опубликована: Ноя. 1, 2024
Язык: Английский
In-depth site-specific glycoproteomic analysis reveals ER-resident protein PDI regulating wheat yellow mosaic virus infection
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
unknown, С. 139303 - 139303
Опубликована: Дек. 1, 2024
Язык: Английский
Simple and efficient enrichment and separation of glycoprotein by teamed boronate affinity magnetic carbon nanospheres
Microchemical Journal,
Год журнала:
2024,
Номер
unknown, С. 111998 - 111998
Опубликована: Окт. 1, 2024
Язык: Английский
Tandem HILIC-IMAC strategy for simultaneous N-glycoproteomics and phosphoproteomics in aging mouse brain
Journal of Chromatography A,
Год журнала:
2024,
Номер
1739, С. 465525 - 465525
Опубликована: Ноя. 15, 2024
Язык: Английский
Integrative cross-omics analysis identifies DNA methylation signatures associated with bilateral hippocampal volume, asymmetry and atrophy rate in the general population
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 21, 2024
Abstract
The
hippocampus
exhibits
volumetric
differences
between
the
left
and
right
hemispheres
(LHCV
RHCV)
asymmetry,
yet
molecular
mechanisms
underlying
these
features
remain
unclear.
In
this
study,
we
performed
a
meta-analysis
of
epigenome-wide
association
studies
(EWAS)
across
six
population-based
cohorts
(n=8,156;
53%
women;
mean
age:
60.7
years)
to
identify
blood-based
methylation
signatures
associated
with
LHCV,
RHCV,
hippocampal
asymmetry.
Integrative
cross-omics
analyses
using
individual-level
genetic,
methylation,
gene
expression
data
(n
>
2,624
participants
from
Rhineland
Study)
revealed
15
CpG/DMR-gene
pairs
linked
LHCV
18
implicating
pathways
involved
in
neuronal
differentiation
immune
processes.
Notably,
baseline
at
loci
predicted
bilateral
atrophy
rates,
explaining
over
10%
variation.
Four
CpGs
were
consistently
asymmetry
cross-sectionally
longitudinally,
exhibiting
sex-specific
differences.
Additionally,
adherence
healthy
dietary
patterns
was
signatures,
highlighting
modifiable
influences
on
health
atrophy.
Язык: Английский