Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(24)
Опубликована: Июнь 5, 2024
Cytoplasmic
mislocalization
and
aggregation
of
TDP-43
protein
are
hallmarks
amyotrophic
lateral
sclerosis
(ALS)
observed
in
the
vast
majority
both
familial
sporadic
cases.
How
these
two
interconnected
processes
regulated
on
a
molecular
level,
however,
remains
enigmatic.
Genome-wide
screens
for
modifiers
ALS-associated
genes
FUS
have
identified
phospholipase
D
(Pld)
pathway
as
key
regulator
ALS-related
phenotypes
fruit
fly
Drosophila
melanogaster
[M.
W.
Kankel
et
al.
,
Genetics
215
747–766
(2020)].
Here,
we
report
results
our
search
downstream
targets
enzymatic
product
Pld,
phosphatidic
acid.
We
identify
conserved
negative
regulators
cAMP/PKA
signaling
pathway,
phosphodiesterase
dunce
inhibitory
subunit
PKA-R2
pathogenic
resulting
from
overexpression
ortholog
TBPH
.
show
that
knockdown
either
mitigation
larval
motor
neuron
cell
bodies,
well
an
amelioration
adult-onset
defects
shortened
lifespan
induced
by
TBPH.
determine
PKA
kinase
activity
is
Pld
target
CrebA
can
rescue
mislocalization.
These
findings
suggest
model
whereby
increasing
ameliorate
functional
effects
pathological
TDP-43.
BioDrugs,
Год журнала:
2023,
Номер
37(1), С. 35 - 55
Опубликована: Янв. 1, 2023
Psoriasis
is
a
systemic
immune-mediated
disease
associated
with
an
increased
risk
of
comorbidities,
such
as
psoriatic
arthritis,
cardiovascular
disease,
metabolic
syndrome,
inflammatory
bowel
psychiatric
disorders,
and
malignancy.
In
recent
years,
the
advent
biological
agents,
efficacy
safety
psoriasis
treatments
have
dramatically
improved.
Presently,
tumor
necrosis
factor-α
inhibitors,
interleukin-17
interleukin-12/23
interleukin-23
inhibitors
are
approved
to
treat
moderate-to-severe
psoriasis.
Small-molecule
apremilast
deucravacitinib,
also
for
treatment
Although
it
still
unclear,
agents
used
significant
impact
on
its
comorbidities
by
altering
state.
Data
from
clinical
trials
studies
biologics
small-molecule
provide
important
information
personalized
care
patients
Notably,
new-onset
or
exacerbations
disease.
addition,
great
caution
needs
be
taken
when
using
in
concomitant
congestive
heart
failure,
multiple
sclerosis,
Apremilast
may
induce
weight
loss
adverse
effect,
presenting
some
beneficial
actions.
A
better
understanding
characteristics
can
more
definitive
guidance
distinct
comorbidities.
Abstract
Rheumatoid
arthritis
(RA)
is
a
chronic
autoimmune
disease
characterized
by
the
unresolved
synovial
inflammation
for
tissues‐destructive
consequence,
which
remains
one
of
significant
causes
disability
and
labor
loss,
affecting
about
0.2–1%
global
population.
Although
treatments
with
disease‐modifying
antirheumatic
drugs
(DMARDs)
are
effective
to
control
decrease
bone
destruction,
overall
remission
rates
RA
still
stay
at
low
level.
Therefore,
uncovering
pathogenesis
expediting
clinical
transformation
imminently
in
need.
Here,
we
summarize
immunological
basis,
inflammatory
pathways,
genetic
epigenetic
alterations,
metabolic
disorders
RA,
highlights
on
abnormality
immune
cells
atlas,
epigenetics,
immunometabolism.
Besides
an
overview
first‐line
medications
including
conventional
DMARDs,
biologics,
small
molecule
agents,
discuss
depth
promising
targeted
therapies
under
or
preclinical
trials,
especially
regulators.
Additionally,
prospects
precision
medicine
based
biopsy
RNA‐sequencing
cell
mesenchymal
stem
chimeric
antigen
receptor
T‐cell
also
looked
forward.
The
advancements
innovations
accelerates
progress
treatments.
Journal of Toxicology and Environmental Health Part B,
Год журнала:
2025,
Номер
unknown, С. 1 - 40
Опубликована: Фев. 27, 2025
Atrazine
is
a
chlorotriazine
herbicide
that
one
of
the
most
widely
used
herbicides
in
USA
and
world.
For
over
60
years
atrazine
has
been
on
major
crops
including
corn,
sorghum,
sugarcane
to
control
broadleaf
grassy
weed
emergence
growth.
exerted
economic
environmental
impact
time,
resulting
reduced
production
costs
increased
conservation
tillage
practices.
However,
widespread
use
long
half-life
led
high
prevalence
environment.
Indeed,
frequent
contaminant
detected
water
sources
USA.
Due
its
almost
ubiquitous
presence
questions
regarding
safety,
well-studied.
First
reported
affect
reproduction
with
potential
disruptive
effects
which
were
later
linked
immune
system,
cancer,
stress
response,
neurological
disorders,
cardiovascular
ailments
experimental
models.
multiple
interwoven
systems
broadens
significance
exposure.
The
endeavor
uncover
mechanisms
underlying
atrazine-induced
dysfunction
mammals
ongoing,
new
genetic
pharmacological
targets
being
reported.
This
review
aims
summarize
prominent
mammalian
physiology,
primarily
focusing
empirical
studies
conducted
lab
animal
models
establish
correlations
epidemiological
human
when
relevant.
In
addition,
current
common
patterns
toxicity
action
will
be
examined.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(5), С. 2911 - 2911
Опубликована: Март 2, 2024
This
paper
delves
into
the
diverse
and
significant
roles
of
curcumin,
a
polyphenolic
compound
from
Curcuma
longa
plant,
in
context
cancer
inflammatory
diseases.
Distinguished
by
its
unique
molecular
structure,
curcumin
exhibits
potent
biological
activities
including
anti-inflammatory,
antioxidant,
potential
anticancer
effects.
The
research
comprehensively
investigates
curcumin’s
interactions
with
key
proteins
involved
progression
response,
primarily
through
docking
studies.
In
cancer,
effectiveness
is
determined
examining
interaction
pivotal
like
CDK2,
CK2α,
GSK3β,
DYRK2,
EGFR,
among
others.
These
suggest
role
impeding
cell
proliferation
survival.
Additionally,
highlights
impact
on
inflammation
influence
such
as
COX-2,
CRP,
PDE4,
MD-2,
which
are
central
to
pathway.
vitro
clinical
studies
extensively
reviewed,
shedding
light
binding
mechanisms,
pharmacological
impacts,
therapeutic
application
various
cancers
conditions.
understanding
functionality
agent.
Conclusively,
this
review
emphasizes
promise
treating
wide
range
health
issues,
attributed
complex
chemistry
broad
properties.
points
towards
growing
importance
multi-faceted
natural
medical
scientific
community.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 10, 2024
Phosphodiesterase
4
(PDE4)
inhibitors
are
effective
therapeutic
agents
for
various
inflammatory
diseases.
Roflumilast,
apremilast,
and
crisaborole
have
been
developed
approved
the
treatment
of
chronic
obstructive
pulmonary
disease
psoriatic
arthritis,
atopic
dermatitis.
Inflammation
underlies
many
vascular
diseases,
yet
role
PDE4
in
these
diseases
remains
inadequately
explored.
This
review
elucidates
clinical
applications
anti-inflammatory
mechanisms
inhibitors,
as
well
their
potential
protective
effects
on
Additionally,
strategies
to
mitigate
adverse
reactions
discussed.
article
emphasizes
need
further
exploration
Molecules,
Год журнала:
2022,
Номер
27(23), С. 8448 - 8448
Опубликована: Дек. 2, 2022
Neurodegenerative
diseases
constitute
a
broad
range
of
central
nervous
system
disorders,
characterized
by
neuronal
degeneration.
Alzheimer’s
disease,
Parkinson’s
amyolotrophic
lateral
sclerosis
(ALS),
and
progressive
forms
multiple
(MS)
are
some
the
most
frequent
neurodegenerative
diseases.
Despite
their
diversity,
these
share
common
pathophysiological
mechanisms:
abnormal
aggregation
disease-related
misfolded
proteins,
autophagosome–lysosome
pathway
dysregulation,
impaired
ubiquitin–proteasome
system,
oxidative
damage,
mitochondrial
dysfunction
excessive
neuroinflammation.
There
is
still
no
effective
drug
that
could
halt
progression
diseases,
current
treatments
mainly
symptomatic.
In
this
regard,
development
novel
multi-target
pharmaceutical
approaches
presents
an
attractive
therapeutic
strategy.
Ibudilast,
anti-inflammatory
firstly
developed
as
asthma
treatment,
cyclic
nucleotide
phosphodiesterases
(PDEs)
inhibitor,
which
acts
increasing
amount
adenosine
monophosphate
(cAMP)
guanosine
(cGMP),
while
downregulating
pro-inflammatory
factors,
such
tumor
necrosis
factor-α
(TNF-α),
macrophage
migration
inhibitory
factor
(MIF)
Toll-like
receptor
4
(TLR-4).
The
preclinical
evidence
shows
ibudilast
may
act
neuroprotectively
in
suppressing
neuroinflammation,
inhibiting
apoptosis,
regulating
function
affecting
pathways,
well
attenuating
stress.
clinical
trials
ALS
MS
also
show
promising
results.
Herein,
we
aim
to
provide
update
on
emerging
potential
discuss
challenges
suggest
future
directions.
