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.
Molecular Medicine,
Год журнала:
2023,
Номер
29(1)
Опубликована: Окт. 25, 2023
Abstract
Autophagy
is
an
explicit
cellular
process
to
deliver
dissimilar
cytoplasmic
misfolded
proteins,
lipids
and
damaged
organelles
the
lysosomes
for
degradation
elimination.
The
mechanistic
target
of
rapamycin
(mTOR)
main
negative
regulator
autophagy.
mTOR
pathway
involved
in
regulating
neurogenesis,
synaptic
plasticity,
neuronal
development
excitability.
Exaggerated
activity
associated
with
temporal
lobe
epilepsy,
genetic
acquired
experimental
epilepsy.
In
particular,
complex
1
(mTORC1)
mainly
epileptogenesis.
investigation
autophagy’s
involvement
epilepsy
has
recently
been
conducted,
focusing
on
critical
role
rapamycin,
autophagy
inducer,
reducing
severity
induced
seizures
animal
model
studies.
induction
could
be
innovative
therapeutic
strategy
managing
Despite
protective
against
epileptogenesis
its
status
epilepticus
(SE)
perplexing
might
beneficial
or
detrimental.
Therefore,
present
review
aims
revise
possible
Journal of Cellular and Molecular Medicine,
Год журнала:
2024,
Номер
28(10)
Опубликована: Май 1, 2024
Parkinson's
disease
(PD)
is
a
neurodegenerative
disorder
of
the
brain
and
manifested
by
motor
non-motor
symptoms
because
degenerative
changes
in
dopaminergic
neurons
substantia
nigra.
PD
neuropathology
associated
with
mitochondrial
dysfunction,
oxidative
damage
apoptosis.
Thus,
modulation
apoptosis
growth
factors
could
be
novel
boulevard
management
PD.
Brain-derived
neurotrophic
factor
(BDNF)
its
receptor
tropomyosin
kinase
type
B
(TrkB)
are
chiefly
involved
neuropathology.
BDNF
promotes
survival
nigra
enhances
functional
activity
striatal
neurons.
Deficiency
TrkB
triggers
degeneration
accumulation
α-Syn
As
well,
BDNF/TrkB
signalling
reduced
early
phase
Targeting
specific
activators
may
attenuate
this
review
aimed
to
discuss
potential
role
against
In
conclusion,
decreased
linked
severity
long-term
complications.
Activation
Nutrients,
Год журнала:
2023,
Номер
15(24), С. 5082 - 5082
Опубликована: Дек. 12, 2023
Endoplasmic
reticulum
(ER)
stress
plays
a
pivotal
role
in
adipogenesis,
which
encompasses
the
differentiation
of
adipocytes
and
lipid
accumulation.
Sustained
ER
has
potential
to
disrupt
signaling
unfolded
protein
response
(UPR),
thereby
influencing
adipogenesis.
This
comprehensive
review
illuminates
molecular
mechanisms
that
underpin
interplay
between
We
delve
into
dysregulation
UPR
pathways,
namely,
IRE1-XBP1,
PERK
ATF6
relation
adipocyte
differentiation,
metabolism,
tissue
inflammation.
Moreover,
we
scrutinize
how
impacts
key
adipogenic
transcription
factors
such
as
proliferator-activated
receptor
γ
(PPARγ)
CCAAT-enhancer-binding
proteins
(C/EBPs)
along
with
their
interaction
other
pathways.
The
cellular
ramifications
include
alterations
adipokines,
aged
adipose
also
discuss
roles
chaperones
cyclophilin
A
B
play
By
shedding
light
on
intricate
relationship
this
paves
way
for
devising
innovative
therapeutic
interventions.
Journal of Cellular and Molecular Medicine,
Год журнала:
2024,
Номер
28(12)
Опубликована: Июнь 1, 2024
Abstract
Parkinson
disease
(PD)
is
one
of
the
most
common
neurodegenerative
diseases
brain.
Of
note,
brain
renin‐angiotensin
system
(RAS)
intricate
in
PD
neuropathology
through
modulation
oxidative
stress,
mitochondrial
dysfunction
and
neuroinflammation.
Therefore,
RAS
by
angiotensin
receptor
blockers
(ARBs)
angiotensin‐converting
enzyme
inhibitors
(ACEIs)
may
be
effective
reducing
risk
neuropathology.
It
has
been
shown
that
all
components
including
peptides
enzymes
are
present
different
areas.
Brain
plays
a
critical
role
regulation
memory
cognitive
function,
controlling
central
blood
pressure.
However,
exaggerated
implicated
pathogenesis
PD.
Two
well‐known
pathways
recognized
including;
classical
pathway
which
mainly
mediated
AngII/AT1R
detrimental
effects.
Conversely,
non‐classical
mostly
ACE2/Ang1‐7/MASR
AngII/AT2R
beneficial
effects
against
Exaggerated
affects
viability
dopaminergic
neurons.
fundamental
mechanism
was
not
fully
elucidated.
Consequently,
purpose
this
review
to
disclose
mechanistic
In
addition,
we
try
revise
how
ACEIs
ARBs
can
developed
for
therapeutics
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Март 14, 2024
Cancer
has
become
a
serious
health
burden
that
results
in
high
incidence
and
mortality
rates
every
year,
mainly
due
to
various
molecular
alterations
inside
the
cell.
Liver
X
receptors
(LXRs)
dysregulation
is
one
among
them
plays
vital
role
cholesterol
metabolism,
lipid
metabolism
inflammation
also
crucial
diseases
such
as
obesity,
metabolic
dysfunction-associated
fatty
liver
disease
(MAFLD),
cardiovascular
diseases,
Type
2
diabetes,
osteoporosis,
cancer.
Studies
report
activation
of
LXRs
inhibits
cancer
growth
by
inhibiting
cellular
proliferation,
inducing
apoptosis
autophagy,
regulating
signalling
pathways
Wnt,
PI3K/AKT,
modulating
expression
levels
cell-cycle
regulators,
promoting
antitumor
immunity
tumor
microenvironment.
In
this
review,
we
have
discussed
role,
structure,
functions
summarized
their
ligands
along
with
mechanism
action.
addition,
cancers,
microenvironment
(TME)
importance
precision
medicine
LXR-targeted
therapies
been
emphasize
potent
targets
for
development
novel
therapeutics.
