medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 14, 2024
Abstract
Recent
advancements
in
Parkinson’s
disease
(PD)
drug
development
have
been
significantly
driven
by
genetic
research.
Importantly,
drugs
supported
evidence
are
more
likely
to
be
approved.
While
genome-wide
association
studies
(GWAS)
a
powerful
tool
nominate
genomic
regions
associated
with
certain
traits
or
diseases,
pinpointing
the
causal
biologically
relevant
gene
is
often
challenging.
Our
aim
was
prioritize
genes
underlying
PD
GWAS
signals.
The
polygenic
priority
score
(PoPS)
similarity-based
prioritization
method
that
integrates
information
from
MAGMA
gene-level
tests
and
than
57,000
features,
including
expression,
biological
pathways,
protein-protein
interactions.
We
applied
PoPS
data
largest
published
East
Asian-
European-ancestries.
identified
120
independent
associations
P
<
5×10
−8
prioritized
46
across
these
loci
based
on
their
scores,
distance
signal,
presence
of
non-synonymous
variants
credible
set.
Alongside
well-established
(
e.g.,
TMEM175
VPS13C
),
some
which
targeted
ongoing
clinical
trials
i.e.
,
SNCA
LRRK2
GBA1
we
plausible
mechanistic
link
pathogenesis
RIT2,
BAG3
SCARB2
).
Many
hold
potential
for
repurposing
novel
therapeutic
developments
i.e.,
FYN,
DYRK1A,
NOD2,
CTSB,
SV2C,
ITPKB
Additionally,
potentially
druggable
relatively
unexplored
XPO1,
PIK3CA,
EP300,
MAP4K4,
CAMK2D,
NCOR1,
WDR43
high-confidence
list
strong
links
may
represent
our
next-best
candidates
disease-modifying
therapeutics.
hope
findings
stimulate
further
investigations
preclinical
work
facilitate
programs.
Neurology and Therapy,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 10, 2025
Epilepsy,
a
prevalent
neurological
disorder
characterized
by
recurrent
seizures,
affects
millions
worldwide,
with
significant
proportion
resistant
to
pharmacological
treatments.
Surgical
interventions
have
emerged
as
pivotal
in
managing
drug-resistant
epilepsy
(DRE),
aiming
reduce
seizure
frequency
or
achieve
freedom.
Traditional
resective
surgeries
evolved
technological
advances,
enhancing
precision
and
safety.
Neurostimulation
techniques,
such
responsive
neurostimulation
(RNS)
deep
brain
stimulation
(DBS),
now
provide
personalized,
real-time
management,
offering
alternatives
traditional
surgery.
Minimally
invasive
ablative
methods,
laser
interstitial
thermal
therapy
(LITT)
Magnetic
Resonance-guided
Focused
Ultrasound
(MRgFUS),
allow
for
targeted
destruction
of
epileptogenic
tissue
reduced
risks
faster
recovery
times.
The
use
stereo-electroencephalography
(SEEG)
robotic
assistance
has
further
refined
surgical
precision,
outcomes.
These
advancements
mark
paradigm
shift
towards
medicine
care,
promising
improved
management
quality
life
patients
globally.
This
review
outlines
the
latest
innovations
surgery,
emphasizing
their
mechanisms
clinical
implications
improve
outcomes
DRE.
Molecules,
Год журнала:
2024,
Номер
29(15), С. 3580 - 3580
Опубликована: Июль 29, 2024
Recent
advancements
in
brain
stimulation
and
nanomedicine
have
ushered
a
new
era
of
therapeutic
interventions
for
psychiatric
neurodegenerative
disorders.
This
review
explores
the
cutting-edge
innovations
techniques,
including
their
applications
alleviating
symptoms
main
disorders
addiction.
Deep
Brain
Stimulation
(DBS)
is
an
FDA-approved
treatment
specific
disorders,
Parkinson's
Disease
(PD),
currently
under
evaluation
other
conditions,
such
as
Alzheimer's
Disease.
technique
has
facilitated
significant
understanding
electrical
circuitry
by
enabling
targeted
providing
insights
into
neural
network
function
dysfunction.
In
reviewing
DBS
studies,
this
places
particular
emphasis
on
underlying
neurotransmitter
modifications
area
location,
particularly
focusing
dopaminergic
system,
which
plays
critical
role
these
conditions.
Furthermore,
delves
groundbreaking
developments
nanomedicine,
highlighting
how
nanotechnology
can
be
utilized
to
target
aberrant
signaling
diseases,
with
focus
system.
The
discussion
extends
emerging
technologies
magnetoelectric
nanoparticles
(MENPs),
represent
novel
intersection
between
nanoformulation
approaches.
These
innovative
offer
promising
avenues
enhancing
precision
effectiveness
treatments
non-invasive,
delivery
agents
well
on-site,
on-demand
stimulation.
By
integrating
from
recent
research
technological
advances,
aims
provide
comprehensive
synergistically
applied
address
complex
neuropsychiatric
paving
way
future
strategies.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(24), С. 13614 - 13614
Опубликована: Дек. 19, 2024
Neuroimmunology
is
reshaping
the
understanding
of
central
nervous
system
(CNS),
revealing
it
as
an
active
immune
organ
rather
than
isolated
structure.
This
review
delves
into
unprecedented
discoveries
transforming
field,
including
emerging
roles
microglia,
astrocytes,
and
blood–brain
barrier
(BBB)
in
orchestrating
neuroimmune
dynamics.
Highlighting
their
dual
both
repair
disease
progression,
we
uncover
how
these
elements
contribute
to
intricate
pathophysiology
neurodegenerative
diseases,
cerebrovascular
conditions,
CNS
tumors.
Novel
insights
microglial
priming,
astrocytic
cytokine
networks,
meningeal
lymphatics
challenge
conventional
paradigms
privilege,
offering
fresh
perspectives
on
mechanisms.
work
introduces
groundbreaking
therapeutic
innovations,
from
precision
immunotherapies
controlled
modulation
BBB
using
nanotechnology
focused
ultrasound.
Moreover,
explore
fusion
with
neuromodulatory
technologies,
underscoring
new
frontiers
for
personalized
medicine
previously
intractable
diseases.
By
synthesizing
advancements,
propose
a
transformative
framework
that
integrates
cutting-edge
research
clinical
translation,
charting
bold
path
toward
redefining
management
era
neuroimmunology.
Neurobiology of Disease,
Год журнала:
2025,
Номер
unknown, С. 106830 - 106830
Опубликована: Фев. 1, 2025
This
study
investigated
the
subthalamic
nucleus
(STN)
function
and
deep
brain
stimulation
(DBS)
effects
on
single-unit
activity
(SUA)
in
Parkinson's
disease
(PD)
patients
with
dysarthria.
After
presurgical
speech
analysis,
we
recorded
STN
neuronal
activities
while
PD
(n
=
16)
articulated
Chinese
Pinyin
consonants.
The
consonants
were
categorized
by
manner
place
of
articulation
for
SUA
cluster
analysis.
cohort
was
then
divided
into
normal
dysarthria
groups
based
diadochokinetic
(DDK)
assessments.
patterns,
represented
mean
firing
rate
(FR),
peak
time,
response
intensity
during
articulation,
analyzed
compared
between
two
groups.
Finally,
a
7
included
to
test
pattern
changes
following
intraoperative
DBS.
Clustering
analysis
patterns
demonstrated
that
neurons
encode
grouping
same
distinct
clusters.
Using
k-means
clustering,
further
classified
SUAs
waveform
types:
negative
spikes
(type
1)
positive
2).
Dysarthria
exhibited
an
increased
FR
type
1
reduced
2
spikes.
During
stimulation,
showed
accelerated
DDK,
accompanied
decrease
increase
FR.
Our
findings
indicate
crucial
role
consonant
encoding
at
level.
Both
DDK
performance
can
be
modulated
Journal of Parkinson s Disease,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 16, 2025
Background
Advances
in
STN-DBS
technology,
among
which
directional
stimulation,
improved
Parkinson's
disease
(PD)
treatment
efficacy,
while
increasing
the
clinical
programming
complexity.
Lead
localization
software
may
aid
stimulation
contact
selection
process.
Objective
We
aimed
to
assess
concordance
between
imaging-suggested
(IGP)
and
conventional-programming
(CP)
selected
contacts
one
year
after
surgery
its
impact
on
motor
outcomes.
Methods
Sixty-four
PD
patients
with
bilateral
were
enrolled.
was
reconstructed
Brainlab
TM
software.
For
each
electrode,
vertical
level
and,
when
applicable,
directionality
predicted
by
lead
reconstruction
be
most
effective
established
compared
parameters
clinically
activated
one-year
post-surgery.
IGP/CP
ratio
calculated
for
both
contacts.
Post-operative
modifications
of
symptoms
severity
groups
concordant
discordant
programming.
Results
One-year
post-surgery,
80%
active
51%
directionality.
No
significant
difference
outcomes
found
activation,
whereas
(c-Direction)
showed
superior
at
follow-up
than
those
(d-Direction)
(UPDRS-III
stimulation-induced
improvement:
c-Direction
=
−25.66
±
13.74
vs.
d-Direction
−12.54
11.86;
p
0.011).
Conclusions
Visual
correctly
levels
patients.
Imaging
therefore
facilitates
classic
assuring
similar
Moreover,
better
reached
parameters,
suggesting
that
visualization
can
represent
an
added
value
particular
npj Parkinson s Disease,
Год журнала:
2025,
Номер
11(1)
Опубликована: Апрель 16, 2025
Abstract
Many
drug
targets
in
ongoing
Parkinson’s
disease
(PD)
clinical
trials
have
strong
genetic
links.
While
genome-wide
association
studies
(GWAS)
nominate
regions
associated
with
disease,
pinpointing
causal
genes
is
challenging.
Our
aim
was
to
prioritize
additional
druggable
underlying
PD
GWAS
signals.
The
polygenic
priority
score
(PoPS)
integrates
information
from
MAGMA
gene-level
associations
and
over
57,000
features.
We
applied
PoPS
East
Asian
European
data
prioritized
based
on
PoPS,
distance
the
signal,
non-synonymous
credible
set
variants.
46
genes,
including
well-established
(
SNCA
,
LRRK2
GBA1
TMEM175
VPS13C
),
literature
evidence
supporting
a
mechanistic
link
RIT2,
BAG3
SCARB2,
FYN,
DYRK1A,
NOD2,
CTSB,
SV2C,
ITPKB
relatively
unexplored
PD.
hold
potential
for
repurposing
or
development.
high-confidence
links
pathogenesis
that
may
represent
our
next-best
candidates
developing
disease-modifying
therapeutics.
Recent
advancements
in
brain
stimulation
and
nanomedicine
have
ushered
a
new
era
of
therapeutic
interventions
for
psychiatric
neurodegenerative
disorders.
This
review
explores
the
cutting-edge
innovations
techniques,
including
their
applications
alleviating
symptoms
main
disorders
addiction.
Emphasis
is
placed
on
underlying
neurotransmitter
modifications
specific
area
location,
particularly
focusing
dopaminergic
system,
which
plays
critical
role
these
conditions.
Furthermore,
delves
into
groundbreaking
developments
nanomedicine,
highlighting
how
nanotechnology
can
be
utilized
to
target
aberrant
signaling
diseases,
with
focus
system.
The
discussion
extends
emerging
technologies
such
as
magnetoelectric
nanoparticles
(MENPs),
represent
novel
intersection
between
nanoformulation
approaches.
These
innovative
offer
promising
avenues
enhancing
precision
effectiveness
treatments
by
enabling
non-invasive,
targeted
delivery
agents
well
site,
on-demand
stimulation.
By
integrating
insights
from
recent
research
technological
advances,
this
aims
provide
comprehensive
understanding
synergistically
applied
address
complex
neuropsychiatric
disorders,
paving
way
future
strategies.