Journal of Agricultural and Food Chemistry,
Год журнала:
2020,
Номер
68(11), С. 3638 - 3648
Опубликована: Фев. 22, 2020
Natural-derived
peptides
are
effective
substances
in
attenuating
oxidative
stress.
However,
their
specific
mechanisms
have
not
been
fully
elucidated,
especially
peptide-mediated
autophagy.
In
the
present
study,
TWLPLPR,
YVLLPSPK,
and
KVPPLLY,
novel
from
Juglans
mandshurica
Maxim,
prevented
reactive
oxygen
species
(ROS)
production,
elevated
glutathione
peroxidase
(GSH-Px)
activity
adenosine
5′-triphosphate
(ATP)
levels,
ameliorated
apoptosis
Aβ25–35
(at
a
concentration
of
50
μM
for
24
h)-induced
PC12
cells
(P
<
0.01).
Both
western
blot
immunofluorescence
analysis
illustrated
that
regulated
Akt/mTOR
signaling
through
p-Akt
(Ser473)
p-mTOR
(S2481)
promoted
autophagy
by
increasing
levels
LC3-II/LC3-I
Beclin-1
while
lowering
p62
expression
The
inhibitor
(3-methyladenine,
3-MA)
inducer
(rapamycin,
RAPA)
were
combined
used
to
confirm
contribution
peptide-regulated
antioxidative
effects.
Moreover,
increased
LAMP1,
LAMP2,
Cathepsin
D
0.05)
fusion
with
lysosomes
form
autolysosomes,
accelerating
ROS
removal.
These
data
suggested
walnut-derived
stress
promoting
Aβ25–35-induced
cells.
Journal of Medicinal Chemistry,
Год журнала:
2022,
Номер
65(24), С. 16033 - 16061
Опубликована: Дек. 12, 2022
The
phosphoinositide
3-kinase
(PI3K)/protein
kinase
B
(AKT)/mammalian
target
of
rapamycin
(mTOR)
pathway
is
one
the
most
important
intracellular
pathways
involved
in
cell
proliferation,
growth,
differentiation,
and
survival.
Therefore,
this
route
a
prospective
biological
for
treating
various
human
diseases,
such
as
tumors,
neurodegenerative
pulmonary
fibrosis,
diabetes.
An
increasing
number
clinical
studies
emphasize
necessity
developing
novel
molecules
targeting
PI3K/AKT/mTOR
pathway.
This
review
focuses
on
recent
advances
ATP-competitive
inhibitors,
allosteric
covalent
proteolysis-targeting
chimeras
against
pathway,
highlights
possible
solutions
overcoming
toxicities
acquired
drug
resistance
currently
available
drugs.
We
also
provide
recommendations
future
design
development
promising
drugs
Molecules,
Год журнала:
2023,
Номер
28(4), С. 1889 - 1889
Опубликована: Фев. 16, 2023
Autism
spectrum
disorder
(ASD)
is
a
complex
neurodevelopmental
characterized
by
impairments
in
social
interaction
and
communication
along
with
repetitive
stereotypic
behaviors.
Currently,
there
are
no
specific
biomarkers
for
diagnostic
screening
or
treatments
available
autistic
patients.
Numerous
genetic
disorders
associated
high
prevalence
of
ASD,
including
tuberous
sclerosis
complex,
phosphatase
tensin
homolog,
fragile
X
syndrome.
Preclinical
investigations
animal
models
these
diseases
have
revealed
irregularities
the
PI3K/Akt/mTOR
signaling
pathway
as
well
ASD-related
behavioral
defects.
Reversal
downstream
molecular
irregularities,
mTOR
hyperactivation,
improved
deficits
observed
preclinical
investigations.
Plant
bioactive
molecules
shown
beneficial
pre-clinical
evidence
ASD
treatment
modulating
pathway.
In
this
review,
we
summarize
involvement
alterations
components
its
critical
impact
on
development
autism
disorder.
Mutations
negative
regulators
mTORC1,
such
TSC1,
TSC2,
PTEN,
result
ASD-like
phenotypes
through
disruption
mTORC1-mediated
signaling.
We
further
discuss
various
naturally
occurring
phytoconstituents
that
been
identified
to
be
modulate
prevent
contribute
therapeutic
effects
ASD.
Biomolecules,
Год журнала:
2019,
Номер
9(11), С. 690 - 690
Опубликована: Ноя. 3, 2019
As
a
group
of
progressive,
chronic,
and
disabling
disorders,
neurodegenerative
diseases
(NDs)
affect
millions
people
worldwide,
are
on
the
rise.
NDs
known
as
gradual
loss
neurons;
however,
their
pathophysiological
mechanisms
have
not
been
precisely
revealed.
Due
to
complex
behind
neurodegeneration,
investigating
effective
multi-target
treatments
has
remained
clinical
challenge.
Besides,
appropriate
neuroprotective
agents
still
lacking,
which
raises
need
for
new
therapeutic
agents.
In
recent
years,
several
reports
introduced
naturally-derived
compounds
promising
alternative
NDs.
Among
natural
entities,
flavonoids
alternatives
affecting
different
pathogenesis
in
neurodegeneration.
Naringenin
is
flavonoid
possessing
activities.
Increasing
evidence
attained
special
attention
variety
targets
along
with
signaling
pathways
naringenin,
suggest
its
possible
applications
Here,
this
review,
effects
well
related
pharmacological
targets,
pathways,
molecular
mechanisms,
perspective,
described.
Moreover,
develop
novel
naringenin
delivery
systems
also
discussed
solve
widespread
pharmacokinetic
limitation.
Rejuvenation Research,
Год журнала:
2016,
Номер
20(3), С. 173 - 182
Опубликована: Ноя. 29, 2016
Metformin,
a
biguanide,
is
widely
used
antidiabetic
drug,
which
inhibits
gluconeogenesis
and
to
treat
hyperglycemia
in
type
2
diabetes.
Through
activation
of
AMPK
(AMP-activated
protein
kinase)
pathway,
metformin
also
mimics
caloric
restriction
health
benefits.
Aging
causes
substantial
molecular
morphological
changes
brain,
the
brain
cells
being
more
susceptible
toward
oxidative
stress
mediated
damages
due
presence
high
lipid
content
higher
oxygen
consumption.
Wistar
rats
(naturally
aged
d-galactose
induced
rat
model)
were
supplemented
with
(300
mg/kg
b.w.
orally)
for
6
weeks.
The
biomarkers
such
as
antioxidant
capacity
(ferric
reducing
potential
[FRAP]),
malondialdehyde
(MDA),
reduced
glutathione
(GSH),
carbonyl
(PCO),
reactive
species
(ROS),
acetylcholinesterase
(AChE)
activity,
nitric
oxide
(NO)
measured
tissues
control
experimental
groups.
results
indicate
that
treatment
augmented
levels
FRAP
GSH
naturally
aged,
d-gal
aging
model
groups
compared
respective
controls.
In
contrast,
treated
exhibited
significant
reduction
MDA,
PCO,
ROS,
NO
increase
AChE
activity
rats.
administration
upregulated
expression
sirtuin-2,
interleukin-6
(IL-6),
tumor
necrosis
factor-alpha
(TNF-α)
downregulated
Beclin-1.
Metformin
supplementation
expressions
IL-6,
TNF-α
expression,
whereas
Beclin-1
expression.
Our
data
confirm
restores
status
improves
healthy
through
autophagy
inflammation.
