Identification of HIBCH and MGME1 as Mitochondrial Dynamics‐Related Biomarkers in Alzheimer's Disease Via Integrated Bioinformatics Analysis
IET Systems Biology,
Год журнала:
2025,
Номер
19(1)
Опубликована: Янв. 1, 2025
ABSTRACT
Mitochondrial
dynamics
(MD)
play
a
crucial
role
in
the
genesis
of
Alzheimer's
disease
(AD);
however,
molecular
mechanisms
underlying
MD
dysregulation
AD
remain
unclear.
This
study
aimed
to
identify
critical
molecules
that
contribute
progression
using
GEO
data
and
bioinformatics
approaches.
The
GSE63061
dataset
comparing
patients
with
healthy
controls
was
analysed,
WGCNA
employed
co‐expression
modules
differentially
expressed
genes
(DEGs)
LASSO
model
developed
verified
DEGs
screen
for
potential
biomarkers.
A
PPI
network
built
predict
upstream
miRNAs,
which
were
experimentally
validated
luciferase
reporter
assays.
total
3518
identified
(2209
upregulated,
1309
downregulated;
|log
2
FC|
>
1.5,
adjusted
p
<
0.05).
revealed
160
MD‐related
genes.
regression
selected
HIBCH
MGME1
as
novel
biomarkers
significant
downregulation
(fold
change
2,
0.001).
KEGG
enrichment
analysis
highlighted
pathways
associated
neurodegeneration.
Luciferase
assays
confirmed
direct
binding
miR‐922
3′UTR
MGME1.
are
promising
diagnostic
AUC
values
0.73
0.74.
Mechanistically,
directly
bind
3′UTR.
Язык: Английский
The Role and Pathogenesis of Tau Protein in Alzheimer’s Disease
Biomolecules,
Год журнала:
2025,
Номер
15(6), С. 824 - 824
Опубликована: Июнь 5, 2025
Alzheimer’s
disease
(AD),
a
predominant
neurodegenerative
disorder,
is
clinically
characterized
by
progressive
cognitive
deterioration
and
behavioral
deficits.
An
in-depth
understanding
of
the
pathogenesis
neuropathology
AD
essential
for
development
effective
treatments
early
diagnosis
techniques.
The
neuropathological
signature
involves
two
hallmark
lesions:
intraneuronal
neurofibrillary
tangles
composed
hyperphosphorylated
tau
aggregates
extracellular
senile
plaques
containing
amyloid-β
(Aβ)
peptide
depositions.
Although
Aβ-centric
research
has
dominated
investigations
over
past
three
decades,
pharmacological
interventions
targeting
Aβ
pathology
have
failed
to
demonstrate
clinical
efficacy.
Tau,
microtubule-associated
protein
predominantly
localized
neuronal
axons,
orchestrates
microtubule
stabilization
axonal
transport
through
dynamic
tubulin
interactions
under
physiological
conditions.
In
pathogenesis,
however,
undergoes
pathogenic
post-translational
modifications
(PTMs),
encompassing
hyperphosphorylation,
lysine
acetylation,
methylation,
ubiquitination,
glycosylation.
These
PTM-driven
alterations
induce
network
disintegration,
mitochondrial
dysfunction,
synaptic
impairment,
neuroinflammatory
cascades,
ultimately
culminating
in
irreversible
neurodegeneration
decline.
This
review
synthesizes
contemporary
advances
PTM
delineates
their
mechanistic
contributions
thereby
establishing
framework
biomarker
discovery,
targeted
therapeutic
development,
precision
medicine
approaches
tauopathies.
solid
theoretical
experimental
basis
diseases,
discovery
targets,
novel
strategies.
Язык: Английский
Accumulation of microtubule-associated protein tau promotes hepatocellular carcinogenesis through inhibiting autophagosome-lysosome fusion
Molecular and Cellular Biochemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 24, 2024
Язык: Английский
Accumulation of microtubule associated protein tau promotes hepatocellular carcinogenesis through inhibiting autophagosome-lysosome fusion
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 11, 2024
Abstract
Dysregulated
expression
of
microtubule
associated
protein
tau
(MAPT)
has
been
reported
in
a
variety
human
cancers.
However,
whether
and
how
MAPT
influences
hepatocellular
carcinogenesis
remains
elusive.
This
study
was
aimed
to
investigate
the
role
underlying
mechanism
proliferation,
invasion,
migration
sorafenib
sensitivity
carcinoma
(HCC)
cells.
An
increased
level
found
primary
tumor
samples
HCC
compared
with
adjacent
normal
liver
tissues,
increase
positively
correlated
p62
evidenced
by
data
obtained
from
The
Cancer
Genome
Atlas
(TCGA),
Gene
Expression
Profiling
Interactive
Analysis
(GEPIA),
patients.
high
also
poorer
survival
patients
demonstrated
using
GEPIA
Kaplan-Meier
analysis.
Further
studies
showed
that
overexpression
promoted
growth,
invasion
decreased
HepG2
Huh7
cells;
accelerated
growth
xenograft
tumors
blockage
autophagosome-lysosome
fusion.
Finally,
overexpressing
inhibited
AMPK,
which
contributed
MAPT-induced
promotion
carcinogenesis.
In
conclusion,
our
provides
proof-of-concept
evidence
validating
as
an
attractive
target.
Язык: Английский