Biomedical & Pharmacology Journal,
Год журнала:
2024,
Номер
17(3), С. 1499 - 1522
Опубликована: Сен. 30, 2024
Studies
have
demonstrated
the
association
between
LXR
activity
dysregulation
with
many
diseases,
including
atherosclerosis,
diabetes
and
cancer.
In
recent
years,
several
agonists
surfaced,
but
none
been
approved
for
human
use
due
to
adverse
effects
or
unforeseen
reasons.
this
study,
we
first
analysed
mRNA
protein
expression
of
LXRs
across
tissues,
network
pathway
analysis,
reinterpreted
their
physiological
function
disease
by
utilizing
multiple
biological
data
repositories,
RNA-seq
atlas,
DisGeNET,
etc.
Then,
performed
ligand-based
virtual
screening,
chemico-pharmacokinetic
docking
simulation
identify
potential
new
compounds.
Our
findings
mRNA,
expression,
enrichment
analysis
reveal
diverse
functions
addressing
possibility
pharmacological
manipulation
small
molecules
would
provide
therapeutic
strategies
management.
Evaluation
properties
directed
selection
LXR-623
AZ876
as
promising
candidates
LXR-α
LXR-β
further
in-silico
investigation.
Comprehensive
screening
ligands
targeting
based
on
chemical
structures
AZ876,
identified
ZINC000005399501
ZINC000021912941
highest
binding
affinity
(−9.8
−10.7
kcal/mol)
LXRα
LXRβ,
respectively.
results
also
supported
in
along
favorable
features.
npj Parkinson s Disease,
Год журнала:
2025,
Номер
11(1)
Опубликована: Янв. 3, 2025
The
relationship
between
hearing
loss
(HL)
and
Parkinson's
disease
(PD)
remains
unclear.
Using
individual-level
summary-level
data
from
the
UK
Biobank
largest
genome-wide
association
studies,
we
examined
this
link
through
observational,
Mendelian
randomization
genetic
pleiotropy
analyses.
Among
158,229
participants,
PD
risk
rose
with
HL
severity
especially
in
elder
males,
aids
significantly
reduced
males.
Although
our
results
did
not
support
a
causal
association,
correlation
analysis
suggested
localized
overlap
(17q21.31).
We
identified
1545
SNPs
63
genes
pleiotropic
effects
on
PD,
including
79
novel
across
6
loci,
3
showing
strong
co-localization.
These
loci
were
enriched
key
tissues
like
brain,
heart,
liver
pancreas,
linked
to
dihydrolipoyl
dehydrogenase
complex
pathway,
targeted
by
drugs
such
as
Warfarin
Phenprocoumon.
Overall,
study
reveals
basis,
connecting
PD.
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 31, 2025
Abstract
Neurodegenerative
disorders
present
significant
challenges
to
modern
medicine
because
of
their
complex
etiology,
pathogenesis,
and
progressive
nature,
which
complicate
practical
treatment
approaches.
Mitochondrial
dysfunction
is
an
important
contributor
the
pathophysiology
various
neurodegenerative
illnesses,
including
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
amyotrophic
lateral
sclerosis
(ALS).
This
review
paper
examines
current
literature
highlighting
multifaceted
functions
mitochondria,
energy
production,
calcium
signaling,
apoptosis
regulation,
mitochondrial
biogenesis,
dynamics,
axonal
transport,
endoplasmic
reticulum–mitochondrial
interactions,
mitophagy,
proteostasis,
crucial
involvement
in
neuronal
health.
The
emphasizes
increasing
recognition
as
a
critical
factor
progression
disorders,
marking
shift
from
traditional
symptom
management
innovative
mitochondrial-based
therapies.
By
discussing
mechanisms,
quality
control
(MQC)
processes
impact
oxidative
stress,
this
highlights
need
for
novel
therapeutic
strategies
restore
function,
protect
connections
integrity,
slow
progression.
comprehensive
aims
provide
insights
into
potential
interventions
that
could
transform
landscape
diseases,
addressing
symptoms
underlying
pathophysiological
changes.
Nutritional Neuroscience,
Год журнала:
2023,
Номер
27(8), С. 870 - 886
Опубликована: Сен. 20, 2023
ABSTRACTParkinson's
disease
(PD)
is
a
chronic
neurodegenerative
(NDD)
due
to
the
degeneration
of
dopaminergic
neurons
(DNs)
in
substantia
nigra
(SN).
PD
characterized
by
diverse
motor
symptoms
such
as
rigidity,
resting
tremors,
and
bradykinesia,
non-motor
cognitive
dysfunction
sleep
disturbances.
Vitamin
D
(VD),
VD
receptor
(VDR),
metabolites
are
present
brain
play
role
maintaining
development,
differentiation,
functions
DNs.
VDRs
exert
protective
effects
against
neuropathology
modulating
functional
capacity
DNs
neurotransmission
SN.
In
virtue
its
anti-inflammatory
antioxidant
activities,
could
be
effective
prevention
treatment
PD.
exerts
neuroprotective
effect
reducing
oxidative
stress
mitochondrial
dysfunction,
increasing
autophagy
brain-derived
neurotrophic
factor
(BDNF).
Low
serum
level
connected
with
development
dementia
The
VD-mediated
augmenting
interrelated
safeguarding
synaptic
plasticity
modulation
neurotransmitter
release.
deficiency
linked
severity
olfactory
which
precedes
progression
symptomatic
However,
precise
remains
unidentified,
there
conflict
about
whether
can
ameliorate
or
not.KEYWORDS:
Parkinson's
diseaseVitamin
DVD
receptorBDNFsubstantia
nigraAutophagyOxidative
stressdopaminergic
AcknowledgementsNot
applicable.Authors'
contributionsAAH
conceptualized
manuscript,
wrote,
edited,
reviewed
main
text
approved
final
edition
manuscript.Disclosure
statementNo
potential
interest
was
reported
author(s).Additional
informationFundingThe
author(s)
no
funding
associated
work
featured
this
article.
