Journal of Integrative Neuroscience,
Год журнала:
2024,
Номер
23(8)
Опубликована: Авг. 12, 2024
Alzheimer’s
disease
(AD)
is
recognized
as
the
leading
cause
of
dementia,
imposing
a
significant
economic
toll
on
society.
Despite
emergence
novel
therapeutic
approaches
for
AD,
their
efficacy
and
safety
mandates
further
validation
through
rigorous
clinical
trials.
In
this
context,
hypertension
(HTN)
has
garnered
considerable
attention
an
amendable
risk
factor
AD.
Research
indicates
that
during
midlife
associated
with
elevated
AD
in
later
years,
influencing
both
onset
progression
disease.
Nevertheless,
relationship
between
stages
life
remains
subject
debate.
Moreover,
consequences
blood
pressure
reduction
cognitive
function,
along
optimal
pharmacological
interventions
thresholds
hypertension,
have
emerged
pivotal
areas
inquiry.
This
review
synthesizes
findings
epidemiology,
neuroimaging,
biomarkers,
effects
antihypertensive
medications
to
elucidate
link
performance.
We
particularly
investigate
how
are
related
by
plasma
sulfide
dysregulation,
offering
possible
indicators
future
diagnosis
therapy.
Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 2067 - 2079
Опубликована: Март 1, 2025
Neurodegenerative
diseases
are
often
linked
to
oxidative
stress
(OS),
which
worsen
neuroinflammation
and
cause
neuronal
damage.
Managing
OS
with
gasotransmitters
such
as
hydrogen
sulphide
(H2S)
is
a
promising
therapeutic
approach
protecting
brain
cells
from
AP39,
mitochondria-targeted
H2S
donor,
has
shown
neuroprotective
potential
by
reducing
improving
mitochondrial
function.
However,
its
clinical
application
limited
due
poor
stability
rapid
release,
necessitating
drug
delivery
system
enhance
efficacy.
This
study
aimed
develop
novel
AP39-loaded
liposomal
formulation
provide
controlled
facilitate
AP39
permeation
across
the
blood-brain
barrier
(BBB),
assess
functional
effects
in
mitigating
preserving
unilamellar
liposomes
were
prepared
via
ethanol
injection
characterised
for
size,
polydispersity,
zeta
potential.
Entrapment
efficiency
was
determined
using
HPLC,
while
cytotoxicity
assessed
human
vein
endothelial
(HUVEC)
neuroblastoma
(SHSY5Y)
cells.
Liposomal
permeability,
release
kinetics,
cellular
uptake
evaluated
microvasculature
BBB
model.
Mitochondrial
function
under
Seahorse
XFe24
Analyzer.
had
an
average
size
of
135.92
±
10.05
nm,
17.35
3.40
mV,
entrapment
84.48%
4.7.
Cytotoxicity
studies
showed
no
adverse
after
4
h.
Cellular
encapsulated
significantly
higher
(7.13
0.28
µg)
than
free
form
(5.8
0.31
µg).
The
model
demonstrated
sustained
(7.28
µg/mL
vs
6.44
AP39).
assays
confirmed
preserved
antioxidant
properties
enhanced
oxygen
consumption.
Our
encapsulating
improves
stability,
promotes
enhances
permeability
effects.
These
findings
indicate
that
suitable
further
investigate
treatment
neurodegenerative
diseases.
Redox Biology,
Год журнала:
2023,
Номер
68, С. 102958 - 102958
Опубликована: Ноя. 6, 2023
Astrocytic
dysfunction
is
central
to
age-related
neurodegenerative
diseases.
However,
the
mechanisms
leading
astrocytic
are
not
well
understood.
We
identify
that
among
diverse
cellular
constituents
of
brain,
murine
and
human
astrocytes
enriched
in
expression
CBS.
Depleting
CBS
causes
mitochondrial
dysfunction,
increases
production
reactive
oxygen
species
(ROS)
decreases
bioenergetics
can
be
partially
rescued
by
exogenous
H
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 17, 2025
AbstractBackground:
Growing
evidence
indicates
that
the
imbalances
in
gut
microbiota
influence
brain
structural
connectivity,
a
key
component
of
microbiota-gut-brain
axis.
However,
deeper
understanding
this
complex
bidirectional
relationship
remains
elusive.
This
study
aims
to
deepen
our
by
examining
underlying
causal
and
mediating
role
inflammatory
cytokines.
Methods:
analyzed
GWAS
data
from
18,340
participants
for
composition
MRI
82,382
connectivity.
We
conducted
two-sample
Mendelian
randomization
(MR)
explore
potential
relationships
between
211
taxa
206
connectivity
features.
A
two-step
mediation
analysis
involving
41
cytokines
was
performed,
using
inverse
variance
weighted
(IVW)
method
as
main
analytical
approach,
supplemented
sensitivity
analyses
reverse
MR
check
robustness,
causation,
heterogeneity,
horizontal
pleiotropy.
Results:
After
Bonferroni
correction,
identified
significant
correlations
11
pairs
traits,
with
6
positive
5
negative
associations.
Reverse
confirmed
associations
nine
pairs.
Sensitivity
found
no
pleiotropy,
or
causality.
Inflammatory
cytokines,
such
RANTES,
HGF,
IL-13,
mediated
10–30%
these
relationships,
mainly
through
JAK-STAT,
IL-17,
MAPK
pathways.
Conclusion:
research
establishes
links
bridging
crucial
gap
axis
research.
These
findings
enhance
suggest
new
therapeutic
targets
neurological
disorders.
Nutrients,
Год журнала:
2025,
Номер
17(9), С. 1597 - 1597
Опубликована: Май 6, 2025
Background:
Neurodegenerative
diseases
(NDDs)
are
multifactorial
disorders
frequently
associated
with
gut
dysbiosis,
oxidative
stress,
and
inflammation;
however,
the
pathophysiological
mechanisms
remain
poorly
understood.
Methods:
Using
untargeted
mass
spectrometry-based
metabolomics
16S
sequencing
of
human
stool,
we
investigated
bacterial
metabolic
dyshomeostasis
in
microbiome
early
disease
stages
across
three
NDDs—amyotrophic
lateral
sclerosis
(ALS),
Alzheimer’s
(AD),
Parkinson’s
(PD)—and
healthy
controls
(HC).
Results:
We
discovered
a
previously
unrecognized
link
between
microbial-derived
metabolite
an
unknown
role
physiology,
2,3-dihydroxypropane-1-sulfonate
(DHPS),
dysbiosis
NDDs.
DHPS
was
downregulated
AD,
ALS,
PD,
while
bacteria
involved
metabolism,
Eubacterium
Desulfovibrio,
were
increased
all
cohorts.
Additionally,
select
taxa
within
Clostridia
class
had
strong
negative
correlations
to
DHPS,
suggesting
potential
metabolism.
A
catabolic
product
is
hydrogen
sulfide,
when
excess,
it
known
promote
inflammation,
mitochondrial
damage,
hallmarks
Conclusions:
These
findings
suggest
that
cryptic
sulfur
metabolism
via
missing
our
current
understanding
NDD
onset
progression.
As
this
hypothesis
generating
study,
more
work
needed
elucidate
neurodegenerative
diseases.
Vascular Pharmacology,
Год журнала:
2023,
Номер
152, С. 107213 - 107213
Опубликована: Авг. 23, 2023
Aging
is
one
of
the
most
promising
risk
factors
for
vascular
diseases,
however,
precise
mechanisms
mediating
aging-related
pathologies
are
not
fully
understood.
Amyloid
beta
(Aβ),
a
peptide
produced
by
proteolytic
processing
amyloid
precursor
protein
(APP),
known
as
key
mediator
brain
damage
involved
in
pathogenesis
Alzheimer's
disease
(AD).
Recently,
it
was
found
that
accumulation
Aβ
wall
linked
to
range
pathologies,
indicating
potential
role
aging-associated
diseases.
In
present
review,
we
have
updated
molecular
regulation
cells
and
tissues,
summarized
relevance
deposition
with
aging
dysregulation
including
impaired
response,
endothelial
dysfunction,
oxidative
stress,
inflammation.
This
review
will
provide
advanced
information
understanding
new
avenue
explore
therapeutic
targets.
