Journal of Controlled Release,
Год журнала:
2024,
Номер
376, С. 470 - 487
Опубликована: Окт. 23, 2024
Alzheimer's
disease
(AD)
is
one
kind
of
devasting
neurodegenerative
disorders
affecting
over
50
million
people
worldwide.
Multi-targeted
therapy
has
emerged
as
a
new
treatment
for
diagnosing
and
alleviating
the
pathogenesis
process
AD;
however,
current
strategy
limited
by
its
unsatisfactory
efficiency.
In
our
study,
engineered
activated
neutrophil-derived
exosomes
(MP@Cur-MExo)
were
developed
to
improve
mitochondrial
function
in
neurons
targeting
Aβ-induced
neurotoxicity.
MP@Cur-MExo
are
derived
from
IL-8-stimulated
neutrophils
decorated
with
mitochondria
ligand
Aβ
targeted
modified
SPION.
Engineered
can
be
cleaved
matrix
metallopeptidase-2,
which
overexpressed
AD
brain.
Consequently,
released
SPION
Curcumin-loaded
collaboratively
protected
neuron
cells
against
deficiency.
addition,
effectively
accumulated
inflamed
region
brain
at
an
early
stage,
allowing
diagnosis
through
bimodal
(MRI/IVIS)
imaging.
Importantly,
mouse
model
stage
AD,
intravenously
injected
restored
reduced
damage,
thereby
attenuating
progression.
conclusion,
designed
demonstrated
that
omnidirectional
improvement
serve
novel
practical
approach
diseases.
This
study
also
reveals
promising
therapeutic
agent
impeding
progression
future
clinical
applications.
Chemical Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 15, 2025
Cytokines
are
crucial
regulators
of
the
immune
system
that
orchestrate
interactions
between
cells
and,
when
dysregulated,
contribute
to
progression
chronic
inflammation,
cancer,
and
autoimmunity.
Numerous
biologic-based
clinical
agents,
mostly
monoclonal
antibodies,
have
validated
cytokines
as
important
targets
now
part
standard
care
for
a
number
diseases.
These
while
impactful,
still
suffer
from
limitations
including
lack
oral
bioavailability,
high
cost
production,
immunogenicity.
Small-molecule
cytokine
inhibitors
attractive
alternatives
can
address
these
limitations.
Although
targeting
cytokine-cytokine
receptor
complexes
with
small
molecules
has
been
challenging
research
endeavor,
multiple
small-molecule
identified,
them
undergoing
evaluation.
In
this
review,
we
highlight
recent
advancements
in
discovery
development
soluble
cytokines.
The
strategies
identifying
novel
ligands
well
structural
mechanistic
insights
into
their
activity
represent
milestones
tackling
clinically
protein-protein
interactions.
Clinical Pharmacology & Therapeutics,
Год журнала:
2024,
Номер
117(2), С. 374 - 386
Опубликована: Окт. 20, 2024
Ketamine
has
a
long
and
very
eventful
pharmacological
history.
Its
enantiomer,
esketamine
((S)‐ketamine),
was
approved
by
the
US
Food
Drug
Administration
(FDA)
EMA
for
patients
with
treatment‐resistant
depression
(TRD)
in
2019.
The
number
of
indications
ketamine
continues
to
increase,
as
well
clinical
trials.
This
analysis
provides
quantitative
overview
use
its
enantiomers
trials
during
2014–2024.
A
total
363
were
manually
assessed
from
clinicaltrial.gov
search
term
“Ketamine.”
highest
found
FDA‐approved
indications:
anesthesia
(~22%)
pain
management
(~28%)
TRD
(~29%).
Clinical
on
both
also
comprised
large
proportion
these
trials,
interestingly,
have
reached
phase
III
IV
status.
Combinatorial
treatment
psychiatric
disorders
non‐psychiatric
conditions
non‐pharmacological
combinations
(electroconvulsive
therapy,
psychotherapeutic
techniques,
virtual
reality,
transcranial
magnetic
stimulation)
is
prevalent.
Sub‐anesthetic
doses
may
represent
novel
therapeutic
avenues
neuropsychiatric
conditions,
that
is,
major
depression,
schizophrenia,
bipolar
disorder,
where
glutamate
excitotoxicity
oxidative
stress
are
likely
be
involved.
study
suggests
studies
will
continue
grow
possible
variants
can
additional
indications.
Journal of Controlled Release,
Год журнала:
2024,
Номер
376, С. 470 - 487
Опубликована: Окт. 23, 2024
Alzheimer's
disease
(AD)
is
one
kind
of
devasting
neurodegenerative
disorders
affecting
over
50
million
people
worldwide.
Multi-targeted
therapy
has
emerged
as
a
new
treatment
for
diagnosing
and
alleviating
the
pathogenesis
process
AD;
however,
current
strategy
limited
by
its
unsatisfactory
efficiency.
In
our
study,
engineered
activated
neutrophil-derived
exosomes
(MP@Cur-MExo)
were
developed
to
improve
mitochondrial
function
in
neurons
targeting
Aβ-induced
neurotoxicity.
MP@Cur-MExo
are
derived
from
IL-8-stimulated
neutrophils
decorated
with
mitochondria
ligand
Aβ
targeted
modified
SPION.
Engineered
can
be
cleaved
matrix
metallopeptidase-2,
which
overexpressed
AD
brain.
Consequently,
released
SPION
Curcumin-loaded
collaboratively
protected
neuron
cells
against
deficiency.
addition,
effectively
accumulated
inflamed
region
brain
at
an
early
stage,
allowing
diagnosis
through
bimodal
(MRI/IVIS)
imaging.
Importantly,
mouse
model
stage
AD,
intravenously
injected
restored
reduced
damage,
thereby
attenuating
progression.
conclusion,
designed
demonstrated
that
omnidirectional
improvement
serve
novel
practical
approach
diseases.
This
study
also
reveals
promising
therapeutic
agent
impeding
progression
future
clinical
applications.
