F1000Research,
Год журнала:
2022,
Номер
11, С. 1176 - 1176
Опубликована: Окт. 17, 2022
Background:
Parkinson's
disease
is
an
attractive
model
to
extend
research
towards
a
better
understanding
of
the
interrelationship
between
genes
and
environment
(exposome)
therefore
ideal
for
polypharmacological
approach
due
its
clinical
heterogeneity.Methods:
In
this
paper,
we
present
series
chemical
scaffolds
extracted
from
ChEMBL
30
Database,
with
two
or
more
targets
PD-related
proteins
obtained
through
chemoinformatics
methods.
This
way,
describe
first
adaptation
Dual
Activity
Difference
(DAD)
map
that
allows
direct
identification
"dual
activity
cliffs".Results:
We
identified
25
antiparkinson
small
molecules
whose
pharmacological
are
directed
dopaminergic
muscarinic
acetyl
choline
M1-M5
receptors;
2
three
norepinephrine
transporter,
D1-D2
6
both
transporter
receptors
1
adenosine
A2a
Dopamine
D1-D5
receptors.Conclusion:
Chemoinformatics
methods
36
related
disease.
Demonstrating
design
drugs
opportunity
in
PD.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Авг. 30, 2024
The
primary
challenge
in
today's
world
of
neuroscience
is
the
search
for
new
therapeutic
possibilities
neurodegenerative
disease.
Central
to
these
disorders
lies
among
other
factors,
aberrant
folding,
aggregation,
and
accumulation
proteins,
resulting
formation
toxic
entities
that
contribute
neuronal
degeneration.
This
review
concentrates
on
key
proteins
such
as
β-amyloid
(Aβ),
tau,
α-synuclein,
elucidating
intricate
molecular
events
underlying
their
misfolding
aggregation.
We
critically
evaluate
mechanisms
governing
elimination
misfolded
shedding
light
potential
strategies.
specifically
examine
pathways
endoplasmic
reticulum
(ER)
unfolded
protein
response
(UPR),
chaperones,
chaperone-mediated
autophagy
(CMA),
intersecting
signaling
Keap1-Nrf2-ARE,
along
with
connected
through
p62.
Above
all,
we
emphasize
significance
quality
control
mechanisms,
encompassing
interventions
targeting
regulation
post-translational
modifications,
enhancement
chaperones
clearance.
Additionally,
focus
current
new,
multi-target
approaches.
In
conclusion,
this
systematically
consolidates
insights
into
emerging
strategies
predicated
aggregates
Chemical Reviews,
Год журнала:
2023,
Номер
123(23), С. 13693 - 13712
Опубликована: Ноя. 17, 2023
An
overview
of
Parkinson's
disease
(PD)
prevalence,
diagnosis,
and
currently
available
treatment
options
is
provided.
A
comprehensive
list
different
classes
marketed
pharmaceutical
drug
products
the
syntheses
various
substances
are
summarized
based
on
published
literature.
Antioxidants,
Год журнала:
2024,
Номер
13(9), С. 1062 - 1062
Опубликована: Авг. 30, 2024
Neurodegenerative
diseases
encompass
a
spectrum
of
disorders
marked
by
the
progressive
degeneration
structure
and
function
nervous
system.
These
conditions,
including
Parkinson's
disease
(PD),
Alzheimer's
(AD),
Huntington's
(HD),
Amyotrophic
lateral
sclerosis
(ALS),
Multiple
(MS),
often
lead
to
severe
cognitive
motor
deficits.
A
critical
component
neurodegenerative
pathologies
is
imbalance
between
pro-oxidant
antioxidant
mechanisms,
culminating
in
oxidative
stress.
The
brain's
high
oxygen
consumption
lipid-rich
environment
make
it
particularly
vulnerable
damage.
Pro-oxidants
such
as
reactive
nitrogen
species
(RNS)
(ROS)
are
continuously
generated
during
normal
metabolism,
counteracted
enzymatic
non-enzymatic
defenses.
In
diseases,
this
balance
disrupted,
leading
neuronal
This
systematic
review
explores
roles
stress,
gut
microbiota,
epigenetic
modifications
aiming
elucidate
interplay
these
factors
identify
potential
therapeutic
strategies.
We
conducted
comprehensive
search
articles
published
2024
across
major
databases,
focusing
on
studies
examining
relationships
redox
homeostasis,
changes
neurodegeneration.
total
161
were
included,
comprising
clinical
trials,
observational
studies,
experimental
research.
Our
findings
reveal
that
stress
plays
central
role
pathogenesis
with
microbiota
composition
significantly
influencing
balance.
Specific
bacterial
taxa
markers
identified
modulators
suggesting
novel
avenues
for
intervention.
Moreover,
recent
evidence
from
human
animal
supports
emerging
concept
targeting
homeostasis
through
therapies.
Future
research
should
focus
validating
targets
settings
exploring
personalized
medicine
strategies
based
individual
profiles.
Clinical Rehabilitation,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 7, 2025
Objective
To
systematically
evaluate
the
efficacy
of
hyperbaric
oxygen
therapy
for
non-motor
symptoms
in
patients
with
Parkinson's
disease.
Data
sources
A
systematic
search
was
performed
across
several
databases,
including
Chinese
Science
and
Technology
Periodical
Database,
Web
Science,
SinoMed,
PubMed,
Cochrane
Library,
Embase
Wanfang
databases
up
to
1
December
2024.
Studies
considered
inclusion
comprised
randomised
controlled
trials
pre–post
control
studies.
Review
methods
The
authors
conducted
data
extraction
literature
screening
procedures
independently.
selected
studies’
quality
evaluated
using
risk
bias
technique.
Manager
5.3
used
conduct
meta-analyses,
while
Stata
15.0
utilised
sensitivity
analysis
assess
publication
bias.
Results
Sixteen
studies
a
total
1324
individuals
satisfied
criteria.
results
meta-analysis
showed
that
significantly
improved
scores
on
Hamilton
Anxiety
Scale
Depression
compared
baseline
(both
p
<
0.05).
Additionally,
improvements
were
observed
Montreal
Cognitive
Assessment,
Mini-Mental
State
Examination,
Disease
Sleep
Scale,
Pittsburgh
Quality
Index,
Kubota's
Drinking
Water
Test
Unified
Rating
III.
Improvements
sleep
efficiency
extension
time
also
noted
controls
(all
Conclusion
findings
indicate
effectively
alleviates
such
as
anxiety,
depression,
cognitive
impairments,
disturbances,
swallowing
dysfunction,
well
improving
motor
function
disease
patients.
Since
protocol
had
significant
differences
between
studies,
further
prospective
rigorous
methodology
are
needed.
Molecules,
Год журнала:
2025,
Номер
30(4), С. 877 - 877
Опубликована: Фев. 14, 2025
Neurodegenerative
diseases
such
as
Alzheimer's
and
Parkinson's
are
among
the
leading
causes
of
physical
cognitive
disability
across
globe.
Fifty
million
people
worldwide
suffer
these
diseases,
that
number
is
expected
to
rise
population
ages.
Ictus
another
pathology
also
courses
with
neurodegeneration
a
cause
mortality
long-term
in
developed
countries.
Schizophrenia
not
common
other
mental
disorders,
affecting
approximately
24
worldwide.
All
disorders
have
still
there
an
effective
pharmacological
treatment
cure
them.
The
N-methyl-D-aspartate
(NMDA)
receptor
(NMDAR)
has
attracted
attention
potential
therapeutic
target
due
its
important
role
learning
memory
implication
excitotoxicity
processes.
Some
drugs
targeting
NMDARs
already
being
used
treat
symptoms
central
nervous
system
(CNS).
Here,
we
aim
review
implications
NMDAR
CNS
pathologies,
target,
future
perspectives
for
developing
new
treatments
focused
on
receptors.
CNS Neuroscience & Therapeutics,
Год журнала:
2025,
Номер
31(2)
Опубликована: Фев. 1, 2025
To
identify
and
validate
causal
protein
targets
that
may
serve
as
potential
therapeutic
interventions
for
both
the
onset
progression
of
Parkinson's
disease
(PD)
through
integrative
proteomic
genetic
analyses.
We
utilized
large-scale
plasma
brain
quantitative
trait
loci
(pQTL)
datasets
from
deCODE
Health
study
Religious
Orders
Study/Rush
Memory
Aging
Project
(ROS/MAP),
respectively.
Proteome-wide
association
studies
(PWAS)
were
conducted
using
OTTERS
framework
proteins
FUSION
tool
proteins,
examining
associations
with
PD
three
phenotypes:
composite,
motor,
cognitive.
Significant
(FDR-corrected
p
<
0.05)
PWAS
further
validated
summary-based
Mendelian
randomization
(SMR),
colocalization
analyses,
reverse
(MR)
to
establish
causality.
Phenome-wide
(PheW-MR)
was
performed
assess
side
effects
across
679
traits
when
targeting
these
reduce
PD-related
phenotype
risk
by
20%.
Additionally,
we
cellular
distribution-based
clustering
gene
expression
data
Allen
Brain
Atlas
(ABA)
explore
distribution
key
regions,
constructed
protein-protein
interaction
(PPI)
networks
via
STRING
database
interactions
among
evaluated
druggability
identified
DrugBank
opportunities
drug
repurposing.
Our
analyses
25
candidate
associated
phenotypes,
including
16
linked
(10
cognitive,
4
3
composite)
9
onset.
Notably,
GPNMB
implicated
in
tissues
PheW-MR
revealed
predominantly
beneficial
targets,
83.7%
indicating
positive
outcomes
16.3%
adverse
effects.
Cellular
categorized
into
distinct
profiles
cell
types
ABA.
PPI
network
analysis
highlighted
one
cluster
cognitive
Druggability
assessment
15
out
had
repurposing
treatment.
have
PD,
providing
new
insights
research
development
treatment
strategies
PD.
