Drug Discovery Today,
Journal Year:
2024,
Volume and Issue:
29(8), P. 104062 - 104062
Published: June 12, 2024
Neurodegenerative
diseases
are
challenging
to
cure.
To
date,
no
cure
has
been
found
for
Alzheimer's
disease
or
Parkinson's
disease,
and
current
treatments
able
only
slow
the
progression
of
manage
their
symptoms.
After
an
introduction
complex
biology
these
diseases,
we
discuss
beneficial
effect
selenium-containing
agents,
which
show
neuroprotective
effects
in
vitro
vivo.
Indeed,
selenium
is
essential
trace
element
that
being
incorporated
into
innovative
organoselenium
compounds,
can
improve
outcomes
rodent
even
primate
models
with
neurological
deficits.
Herein,
critically
recent
findings
field
selenium-based
applications
disorders.
Neural Regeneration Research,
Journal Year:
2022,
Volume and Issue:
17(11), P. 2342 - 2342
Published: Jan. 1, 2022
Alzheimer's
disease,
the
most
common
type
of
dementia
among
older
adults,
currently
cannot
be
prevented
or
effectively
treated.
Only
a
very
small
percentage
disease
cases
have
an
established
genetic
cause.
The
majority
lack
clear
causative
event,
but
several
modifiable
factors
been
associated
with
increased
risk
this
disease.
Persistent
midlife
hypertension
is
one
such
factor,
which
can
controlled
through
changes
in
diet,
lifestyle,
and
antihypertensive
drugs.
Identifying
molecular
mechanisms
linking
could
enhance
our
understanding
lead
to
identification
novel
targets
therapeutic
approaches
for
effective
treatments.
Glial
cell-driven
neuroinflammation
key
pathological
features
In
review,
we
illustrate
that
also
possible
Animal
studies
demonstrated
chronically
elevated
blood
pressure
leads
adverse
glial
activation
brain
inflammatory
mediators.
We
highlight
damage
cerebral
microvasculature
locally
activated
renin-angiotensin
system
as
pathogenetic
accompanying
neurodegeneration.
role
tumor
necrosis
factor-α
interleukin-1β
pro-inflammatory
signaling
molecules
providing
link
discussed.
summarize
available
experimental
data
indicating
neuroinflammatory
reversed
by
different
classes
medicines.
These
suggest
antihypertensives
beneficial
not
only
due
their
ability
control
pressure,
anti-neuroinflammatory
effects.
Confirmation
these
observations
human
subjects
required
recent
advances
imaging
techniques
allowing
visualization
both
microglia
astrocyte
will
essential
research.
Frontiers in Aging Neuroscience,
Journal Year:
2022,
Volume and Issue:
14
Published: June 24, 2022
Alzheimer's
disease
(AD)
is
a
complex
neurodegenerative
disorder.
The
relative
contribution
of
the
numerous
underlying
functional
mechanisms
poorly
understood.
To
comprehensively
understand
context
and
distribution
pathways
that
contribute
to
AD,
we
performed
text-mining
generate
an
exhaustive,
systematic
assessment
breadth
diversity
biological
within
corpus
206,324
dementia
publication
abstracts.
A
total
91%
(325/335)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
have
publications
containing
association
via
at
least
5
studies,
while
63%
pathway
terms
50
studies
providing
clear
with
AD.
Despite
major
technological
advances,
same
set
top-ranked
been
consistently
related
AD
for
30
years,
including
immune
system,
metabolic
pathways,
cholinergic
synapse,
long-term
depression,
proteasome,
diabetes,
cancer,
chemokine
signaling.
studied
appear
biased:
animal
model
human
subject
prioritize
different
pathways.
Surprisingly,
genetic
discoveries
drug
targeting
are
not
enriched
in
most
frequently
Our
findings
suggest
only
this
disorder
incredibly
complex,
but
its
reach
also
nearly
global.
As
consequence
our
study,
research
results
can
now
be
assessed
wider
literature,
supporting
design
therapies
target
broader
range
mechanisms.
study
explored
www.adpathways.org.
Journal of Alzheimer s Disease,
Journal Year:
2024,
Volume and Issue:
98(2), P. 643 - 657
Published: March 1, 2024
Background:
Alzheimer’s
disease
(AD)
is
a
chronic
neurodegenerative
needing
effective
therapeutics
urgently.
Sildenafil,
one
of
the
approved
phosphodiesterase-5
inhibitors,
has
been
implicated
as
having
potential
effect
in
AD.
Objective:
To
investigate
therapeutic
benefit
sildenafil
on
Methods:
We
performed
real-world
patient
data
analysis
using
MarketScan®
Medicare
Supplemental
and
Clinformatics®
databases.
conducted
propensity
score-stratified
analyses
after
adjusting
confounding
factors
(i.e.,
sex,
age,
race,
comorbidities).
used
both
familial
sporadic
AD
induced
pluripotent
stem
cells
(iPSC)
derived
neurons
to
evaluate
sildenafil’s
mechanism-of-action.
Results:
showed
that
usage
associated
with
reduced
likelihood
across
four
new
drug
compactor
cohorts,
including
bumetanide,
furosemide,
spironolactone,
nifedipine.
For
instance,
54%
incidence
(hazard
ratio
[HR]
=
0.46,
95%
CI
0.32–
0.66)
30%
prevalence
(HR
0.70,
0.49–
1.00)
compared
spironolactone.
found
treatment
tau
hyperphosphorylation
(pTau181
pTau205)
dose-dependent
manner
iPSC-derived
neurons.
RNA-sequencing
sildenafil-treated
reveals
specifically
target
related
genes
pathobiological
pathways,
mechanistically
supporting
beneficial
Conclusions:
These
validation
mechanistic
observations
from
further
suggested
repurposable
for
Yet,
randomized
clinical
trials
are
warranted
validate
causal
effects
Drug Discovery Today,
Journal Year:
2024,
Volume and Issue:
29(8), P. 104062 - 104062
Published: June 12, 2024
Neurodegenerative
diseases
are
challenging
to
cure.
To
date,
no
cure
has
been
found
for
Alzheimer's
disease
or
Parkinson's
disease,
and
current
treatments
able
only
slow
the
progression
of
manage
their
symptoms.
After
an
introduction
complex
biology
these
diseases,
we
discuss
beneficial
effect
selenium-containing
agents,
which
show
neuroprotective
effects
in
vitro
vivo.
Indeed,
selenium
is
essential
trace
element
that
being
incorporated
into
innovative
organoselenium
compounds,
can
improve
outcomes
rodent
even
primate
models
with
neurological
deficits.
Herein,
critically
recent
findings
field
selenium-based
applications
disorders.
