Medicina,
Journal Year:
2024,
Volume and Issue:
60(11), P. 1805 - 1805
Published: Nov. 3, 2024
Background
and
Objectives:
Alzheimer’s
disease
(AD)
is
the
most
common
neurodegenerative
disorder
in
world.
Due
to
failure
of
traditional
drugs
produce
a
complete
cure
for
AD,
search
new
safe
effective
lines
therapy
has
attracted
attention
ongoing
research.
Canagliflozin
an
anti-diabetic
agent
with
proven
efficacy
treatment
neurological
disorders
which
mitochondrial
dysfunction,
oxidative
stress,
apoptosis,
autophagy
play
pathophysiological
role.
Elucidation
potential
effects
different
doses
canagliflozin
on
AD
induced
by
aluminium
chloride
rats
exploration
molecular
mechanisms
that
may
contribute
these
were
primary
objectives
current
study.
Materials
Methods:
In
rat
model
effect
three
behavioural,
biochemical,
histopathological
alterations
was
assessed.
Results:
administered
chloride-treated
animals
dose-dependent
normalisation
behavioural
tests,
augmentation
antioxidant
defence
mechanisms,
inhibition
TXNIP/NLRP3
inflammasome
signalling,
modulation
SIRT1/HMGB1
axis,
interference
pro-inflammatory
pro-apoptotic
restoration
functions
hippocampal
tissues
approximately
baseline
values.
addition,
exhibited
interesting
ability
repress
chloride-induced
changes
brain.
Conclusions:
The
functions,
inflammatory
pathways,
signals
open
gates
towards
mitigation
pathologic
features
AD.
Archiv der Pharmazie,
Journal Year:
2024,
Volume and Issue:
357(9)
Published: May 30, 2024
Abstract
Urokinase‐type
plasminogen
activator
(PLAU),
a
member
of
the
S1
serine
peptidase
family
in
Clan
PA,
plays
crucial
role
conversion
into
active
plasmin.
However,
precise
PLAU
central
nervous
system
remains
incompletely
elucidated,
particularly,
relation
to
Alzheimer's
disease
(AD).
In
this
study,
we
successfully
identified
that
could
promote
cell
senescence
neurons,
indicating
it
as
potential
target
for
AD
treatment
through
systematic
approach,
which
included
both
bioinformatics
analysis
and
experimental
verification.
Subsequently,
structure‐based
virtual
screening
approach
was
employed
identify
inhibitor
from
Food
Drug
Administration‐approved
drug
database.
After
analyzing
docking
scores
thoroughly
examining
receptor–ligand
complex
interaction
modes,
vilazodone
emerges
highly
promising
inhibitor.
Additionally,
molecular
dynamics
simulations
were
performed
generate
structure
between
relatively
stable
PLAU.
Of
note,
exhibited
superior
cytotoxicity
against
senescent
cells,
showing
senolytic
activity
targeting
ultimately
producing
an
anti‐AD
effect.
These
findings
suggest
represent
therapeutic
strategy
AD.
Furthermore,
investigating
inhibitory
structural
modifications
based
on
may
provide
valuable
insights
future
development
disorders.
Medicina,
Journal Year:
2024,
Volume and Issue:
60(11), P. 1812 - 1812
Published: Nov. 4, 2024
Rosiridin
is
a
monoterpene
with
outstanding
monoamine
inhibitory
activity
that
useful
to
treat
depressive
episodes
and
rapid-onset
dementia.
The
current
investigation
aims
evaluate
the
neurologically
protective
impact
of
rosiridin,
which
opposes
aluminum
chloride
(AlCl
Medicina,
Journal Year:
2024,
Volume and Issue:
60(11), P. 1805 - 1805
Published: Nov. 3, 2024
Background
and
Objectives:
Alzheimer’s
disease
(AD)
is
the
most
common
neurodegenerative
disorder
in
world.
Due
to
failure
of
traditional
drugs
produce
a
complete
cure
for
AD,
search
new
safe
effective
lines
therapy
has
attracted
attention
ongoing
research.
Canagliflozin
an
anti-diabetic
agent
with
proven
efficacy
treatment
neurological
disorders
which
mitochondrial
dysfunction,
oxidative
stress,
apoptosis,
autophagy
play
pathophysiological
role.
Elucidation
potential
effects
different
doses
canagliflozin
on
AD
induced
by
aluminium
chloride
rats
exploration
molecular
mechanisms
that
may
contribute
these
were
primary
objectives
current
study.
Materials
Methods:
In
rat
model
effect
three
behavioural,
biochemical,
histopathological
alterations
was
assessed.
Results:
administered
chloride-treated
animals
dose-dependent
normalisation
behavioural
tests,
augmentation
antioxidant
defence
mechanisms,
inhibition
TXNIP/NLRP3
inflammasome
signalling,
modulation
SIRT1/HMGB1
axis,
interference
pro-inflammatory
pro-apoptotic
restoration
functions
hippocampal
tissues
approximately
baseline
values.
addition,
exhibited
interesting
ability
repress
chloride-induced
changes
brain.
Conclusions:
The
functions,
inflammatory
pathways,
signals
open
gates
towards
mitigation
pathologic
features
AD.
