Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Июль 10, 2024
Huntington’s
disease
(HD)
is
caused
by
an
expansion
of
CAG
trinucleotide
repeat
in
the
HTT
gene;
exact
pathogenesis
HD
currently
remains
unclear.
One
promising
directions
study
HDs
to
determine
molecular
mechanism
underlying
development
and
role
microRNAs
(miRNAs).
This
aimed
identify
profile
miRNAs
human
cell
line
model
as
diagnostic
biomarkers
for
HD.
To
HD,
SH-SY5Y
based
on
expression
two
different
forms:
pEGFP-Q23
pEGFP-Q74
HTT.
The
Htt
protein
was
confirmed
using
aggregation
assays
combined
with
immunofluorescence
Western
blotting
methods.
miRNA
levels
were
measured
neuronal
samples
stably
expressing
Q23
Q74
extraction-free
HTG
EdgeSeq
protocol.
A
total
2083
detected,
354
(top
18
miRNAs)
significantly
differentially
expressed
(DE)
(
p
<
0.05)
lines.
majority
downregulated
model.
Moreover,
we
revealed
that
six
DE
target
seven
genes
ATN1,
GEMIN4,
EFNA5
,
CSMD2,
CREBBP,
ATXN1,
B3GNT
)
play
important
roles
neurodegenerative
disorders
showed
significant
differences
mutant
(Q74)
when
compared
wild-type
(Q23)
RT-qPCR
0.05
0.01).
We
demonstrated
most
miRNA-mRNA
profiles,
interaction
binding
sites,
their
related
pathways
experimental
bioinformatics
will
allow
novel
strategies
provide
alternative
therapeutic
routes
treating
Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Янв. 9, 2024
Alzheimer's
disease
(AD)
is
the
most
prevalent
form
of
dementia
in
elderly
and
represents
a
major
clinical
challenge
ageing
society.
Neuropathological
hallmarks
AD
include
neurofibrillary
tangles
composed
hyperphosphorylated
tau,
senile
plaques
derived
from
deposition
amyloid-β
(Aβ)
peptides,
brain
atrophy
induced
by
neuronal
loss,
synaptic
dysfunctions.
Death-associated
protein
kinase
1
(DAPK1)
ubiquitously
expressed
central
nervous
system.
Dysregulation
DAPK1
has
been
shown
to
contribute
various
neurological
diseases
including
AD,
ischemic
stroke
Parkinson's
(PD).
We
have
established
an
upstream
effect
on
Aβ
tau
pathologies
apoptosis
through
kinase-mediated
phosphorylation,
supporting
causal
role
pathophysiology
AD.
In
this
review,
we
summarize
current
knowledge
about
how
involved
pathological
changes
hyperphosphorylation,
deposition,
cell
death
degeneration.
The
underlying
molecular
mechanisms
dysregulation
are
discussed.
also
review
recent
progress
regarding
development
novel
modulators
their
potential
applications
intervention.
These
findings
substantiate
as
therapeutic
target
for
multifunctional
disease-modifying
treatments
other
disorders.
Molecular Psychiatry,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 11, 2024
In
the
context
of
escalating
global
health
challenge
posed
by
Alzheimer's
disease
(AD),
this
comprehensive
review
considers
potential
melatonin
in
both
preventive
and
therapeutic
capacities.
As
a
naturally
occurring
hormone
robust
antioxidant,
accumulating
evidence
suggests
is
compelling
candidate
to
consider
AD-related
pathologies.
The
several
mechanisms,
including
effects
on
amyloid-beta
pathologic
tau
burden,
antioxidant
defense,
immune
modulation,
regulation
circadian
rhythms.
Despite
its
promise,
gaps
need
be
addressed
prior
clinical
translation.
These
include
conducting
additional
randomized
trials
patients
with
or
at
risk
for
AD
dementia,
determining
optimal
dosage
timing,
further
side
effects,
particularly
long-term
use.
This
consolidates
existing
knowledge,
identifies
gaps,
directions
future
research
better
understand
neuroprotection
mitigation
within
landscape
AD.
Frontiers in Cellular Neuroscience,
Год журнала:
2022,
Номер
16
Опубликована: Июль 28, 2022
Neurological
disorders
are
a
group
of
with
motor,
sensory
or
cognitive
damage,
caused
by
dysfunction
the
central
peripheral
nervous
system.
Cyclin-dependent
kinases
5
(Cdk5)
is
vital
significance
for
development
system,
including
migration
and
differentiation
neurons,
formation
synapses,
axon
regeneration.
However,
when
system
subject
to
pathological
stimulation,
aberrant
activation
Cdk5
will
induce
abnormal
phosphorylation
variety
substrates,
resulting
in
cascade
signaling
pathway,
thus
lead
changes.
intimately
related
mechanism
neurological
disorders,
such
as
A-β
protein
Alzheimer’s
disease,
mitochondrial
fragmentation
cerebral
ischemia,
apoptosis
dopaminergic
neurons
Parkinson’s
disease.
It
worth
noting
that
inhibitors
have
been
reported
neuroprotective
effects
inhibiting
processes.
Therefore,
this
review,
we
briefly
introduce
physiological
mechanisms
focusing
on
recent
advances
prospect
targeted
treatment
disorders.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(22), С. 16259 - 16259
Опубликована: Ноя. 13, 2023
Alzheimer’s
disease
(AD)
is
a
complex
multifactorial
disorder
that
poses
substantial
burden
on
patients,
caregivers,
and
society.
Considering
the
increased
aging
population
life
expectancy,
incidence
of
AD
will
continue
to
rise
in
following
decades.
However,
molecular
pathogenesis
remains
controversial,
superior
blood-based
biomarker
candidates
for
early
diagnosis
are
still
lacking,
effective
therapeutics
halt
or
slow
progression
urgently
needed.
As
powerful
genetic
regulators,
microRNAs
(miRNAs)
receiving
increasing
attention
due
their
implications
initiation,
development,
theranostics
various
diseases,
including
AD.
In
this
review,
we
summarize
miRNAs
directly
target
microtubule-associated
protein
tau
(MAPT),
amyloid
precursor
(APP),
β-site
APP-cleaving
enzyme
1
(BACE1)
transcripts
regulate
alternative
splicing
APP.
We
also
discuss
related
kinases,
such
as
glycogen
synthase
kinase
(GSK)-3β,
cyclin-dependent
5
(CDK5),
death-associated
(DAPK1),
well
apolipoprotein
E,
targeted
by
control
phosphorylation
amyloidogenic
APP
processing
leading
Aβ
pathologies.
Moreover,
there
evidence
miRNA-mediated
modulation
inflammation.
Furthermore,
circulating
serum
plasma
patients
noninvasive
biomarkers
with
diagnostic
potential
reviewed.
addition,
miRNA-based
optimized
nanocarriers
exosomes
options
treatment
discussed.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(14), С. 7992 - 7992
Опубликована: Июль 20, 2022
The
neuropathology
of
Alzheimer’s
disease
(AD)
is
characterized
by
intracellular
aggregation
hyperphosphorylated
tau
and
extracellular
accumulation
beta-amyloid
(Aβ).
Death-associated
protein
kinase
1
(DAPK1),
as
a
novel
therapeutic
target,
shows
promise
for
the
treatment
human
AD,
but
regulatory
mechanisms
DAPK1
expression
in
AD
remain
unclear.
In
this
study,
we
identified
miR-143-3p
promising
candidate
targeting
DAPK1.
directly
bound
to
3′
untranslated
region
mRNA
inhibited
its
translation.
decreased
phosphorylation
promoted
neurite
outgrowth
microtubule
assembly.
Moreover,
attenuated
amyloid
precursor
(APP)
reduced
generation
Aβ40
Aβ42.
Furthermore,
restoring
with
antagonized
effects
attenuating
hyperphosphorylation
Aβ
production.
addition,
levels
were
downregulated
correlated
inversely
hippocampus
patients.
Our
results
suggest
that
might
play
critical
roles
regulating
both
aberrant
amyloidogenic
processing
APP
thus
offer
potential
strategy
AD.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(24), С. 17295 - 17295
Опубликована: Дек. 9, 2023
Alzheimer’s
disease
(AD)
is
currently
the
most
common
neurodegenerative
disease.
Glycogen
synthase
kinase
3β
(GSK-3β)
a
pivotal
factor
in
AD
pathogenesis.
Recent
research
has
demonstrated
that
plant
miRNAs
exert
cross-kingdom
regulation
on
target
genes
animals.
Gastrodia
elata
(G.
elata)
valuable
traditional
Chinese
medicine
significant
pharmacological
activity
against
diseases
of
central
nervous
system
(CNS).
Our
previous
studies
have
indicated
G.
elata-specific
miRNA
plays
regulatory
role
for
NF-κB
signaling
pathway
mice.
In
this
study,
further
bioinformatics
analysis
suggested
Gas-miR36-5p
targets
GSK-3β.
Through
western
blot,
RT-qPCR,
and
assessments
T-AOC,
SOD,
MDA
levels,
its
neuroprotective
effects
an
cell
model.
Furthermore,
was
detected
murine
brain
tissues.
The
results
Morris
water
maze
test
blot
provided
positive
evidence
reversing
learning
deficits
hyperphosphorylation
Tau
mice,
elucidating
model
following
RNA
administration.
emphasizes
as
novel
with
properties
by
targeting
Consequently,
our
findings
provide
insights
into
mechanisms
underlying
miRNA,
presenting
perspective
treatment
