Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 11, 2023
Abstract
Alzheimer’s
disease
(AD),
is
the
most
prevalent
cause
of
dementia,
with
no
effective
treatment
thus
far.
It
clear
that
tau
protein
hyperphosphorylation
major
pathogenic
process,
leading
to
neurodegeneration
upon
AD.
has
been
previously
shown
phosphorylation
at
Thr231
crucial
importance
in
tauopathy
process.
was
reported
pT231-tau
cis
conformation
early
driver
pathogenicity
mouse
models.
In
this
study,
we
identified
gauche
P-tau
pathology
(a
novel
conformer)
human
postmortem
brain
tissue
and
as
well
induced
pluripotent
stem
cell
(iPSC)
derived
neurons
from
AD
patients
neurotoxic
conformer.
We
observed
levels
dramatically
increase
under
aging
stress
which
disrupts
microtubule
network,
propagates
other
neurons,
ultimately
leads
apoptosis
death.
Moreover,
while
p-tau
depletion
using
respective
monoclonal
antibody
suppressed
elimination
stopped
cultured
neurons.
Taken
these
together,
concluded
neuronal
death
anti
could
be
introduced
an
efficient
therapeutic
for
blocking
Antioxidants,
Journal Year:
2024,
Volume and Issue:
13(4), P. 433 - 433
Published: April 2, 2024
Our
study
aimed
to
explore
the
impact
and
mechanism
of
Euonymus
alatus
leaf
extract
on
age-dependent
oxidative
stress,
neuroinflammation,
progressive
memory
impairments
in
aged
mice.
Twenty-four-month-old
mice
received
EA-L3
(300
mg/kg/day)
or
reference
drug,
donepezil
(DPZ,
5
mg/kg/day),
for
6
weeks,
learning
functions
were
detected
using
Passive
Avoidance
Test
(PAT).
As
expected,
cognitive
function
deficits
compared
with
young
mice,
these
significantly
mitigated
by
dietary
treatments
EA-L3.
In
parallel,
it
upregulated
brain-derived
neurotrophic
factor
(BDNF)
subsequently
activated
extracellular-signal-regulated
kinase
(ERK)/cAMP
response
element-binding
(CREB)
signaling
mouse
hippocampus
scopolamine-induced
B35
SH-SY5Y
neuroblastoma
cells.
showed
strong
anti-inflammatory
effects
decreased
NF-κBp65,
cyclooxygenase
2
(COX-2),
tumor
necrosis
alpha
(TNF-α),
increased
interleukin
(IL)-10,
doublecortin
(DCX)
protein
expression
Similar
results
also
confirmed
LPS-induced
BV-2
microglia
cells
upon
treatment
extract.
addition,
notably
dose-dependently
ROS
BV2
after
exposure
LPS.
Taken
together,
might
be
used
as
a
supplement
alleviate
deterioration
hippocampal-based
tasks,
neuroinflammation
elderly
people.
Aging Cell,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 25, 2024
Abstract
Aging
is
an
intricate
process
involving
interactions
among
multiple
factors,
which
one
of
the
main
risks
for
chronic
diseases,
including
Alzheimer's
disease
(AD).
As
a
member
cysteine
protease,
cathepsin
S
(CTSS)
has
been
implicated
in
inflammation
across
various
diseases.
Here,
we
investigated
role
neuronal
CTSS
aging
and
AD
started
by
examining
expression
hippocampus
neurons
mice
identified
significant
increase,
was
negatively
correlated
with
recognition
abilities.
Concurrently,
observed
elevation
concentration
serum
elderly
people.
Transcriptome
fluorescence‐activated
cell
sorting
(FACS)
results
revealed
that
overexpression
aggravated
brain
inflammatory
milieu
microglia
activation
to
M1
pro‐inflammatory
phenotype,
chemokine
C‐X3‐C‐motif
ligand
1
(CX3CL1)—chemokine
receptor
(CX3CR1)
axis
janus
kinase
2
(JAK2)—signal
transducer
activator
transcription
3
(STAT3)
pathway.
CX3CL1
secreted
acts
on
CX3CR1
microglia,
our
first
time
neuron
neuron–microglia
“crosstalk.”
Besides,
elevated
regions
patients,
hippocampus.
Utilizing
selective
inhibitor,
LY3000328,
rescued
AD‐related
pathological
features
APP/PS1
mice.
We
further
noticed
increased
B
(CTSB)
activity,
but
decreased
L
(CTSL)
activity
microglia.
Overall,
provide
evidence
can
be
used
as
biomarker
plays
regulatory
roles
through
modulating
neuroinflammation
process.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(4), P. 1590 - 1590
Published: Feb. 13, 2025
As
the
world's
population
continues
to
age,
social
patterns
are
changing,
making
aging
a
notable
public
health
challenge.
With
as
major
risk
factor
for
cognitive
decline,
global
prevalence
of
dementia
is
projected
triple
in
next
25
years.
In
light
growing
body
evidence
involvement
microbiota
and
pathology,
its
role
age-related
decline
should
be
explored.
Therefore,
aim
this
narrative
review
thoroughly
analyze
ways
which
might
affect
process
decline.
Overall,
complex
phenomenon
manifested
at
systemic,
cellular
molecular
levels.
According
recent
studies,
gut
composition
may
influence
changes
through
gut-brain
axis.
One
mechanism
involves
dysbiosis-related
chronic
systemic
inflammation,
leading
blood-brain
barrier
disruption
subsequent
neuroinflammatory
processes.
addition
inflammaging,
induce
oxidative
stress,
another
key
brain
aging.
Finally,
not
only
microbiota,
but
also
colonizing
oral
cavity
associated
with
neurodegenerative
diseases.
Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
17(3), P. 284 - 284
Published: Feb. 20, 2025
Cognitive
aging,
characterized
by
the
gradual
decline
in
cognitive
functions
such
as
memory,
attention,
and
problem-solving,
significantly
impacts
daily
life.
This
is
often
accelerated
neurodegenerative
diseases,
particularly
Alzheimer’s
Disease
(AD)
Parkinson’s
(PD).
AD
marked
accumulation
of
amyloid-beta
plaques
tau
tangles,
whereas
PD
involves
degeneration
dopaminergic
neurons.
Both
conditions
lead
to
severe
impairment,
greatly
diminishing
quality
life
for
affected
individuals.
Recent
advancements
regenerative
medicine
have
highlighted
mesenchymal
stromal
cells
(MSCs)
their
derived
exosomes
promising
therapeutic
options.
MSCs
possess
regenerative,
neuroprotective,
immunomodulatory
properties,
which
can
promote
neurogenesis,
reduce
inflammation,
support
neuronal
health.
Exosomes,
nanosized
vesicles
from
MSCs,
provide
an
efficient
means
delivering
bioactive
molecules
across
blood–brain
barrier,
targeting
underlying
pathologies
PD.
While
these
therapies
hold
great
promise,
challenges
variability
MSC
sources,
optimal
dosing,
effective
delivery
methods
need
be
addressed
clinical
application.
The
development
robust
protocols,
along
with
rigorous
trials,
crucial
validating
safety
efficacy
exosome
therapies.
Future
research
should
focus
on
overcoming
barriers,
optimizing
treatment
strategies,
exploring
integration
lifestyle
interventions.
By
addressing
challenges,
MSC-
exosome-based
could
offer
transformative
solutions
improving
outcomes
enhancing
individuals
aging
diseases.
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: March 8, 2025
Despite
extensive
research
on
neuroimaging
correlates
of
human
brain
aging,
there
is
little
mechanistic
insight
into
how
they
are
linked
to
loss
function.
Previous
studies
the
role
cerebral
blood
flow
(CBF)
in
supporting
function
have
focused
delivery
nutrients,
namely
oxygen
and
glucose.
However,
CBF
required
also
clear
byproducts
energy
metabolism,
CO2
protons.
With
goal
determining
whether
age-associated
reduction
regional
may
lead
abnormal
partial
pressure
carbon
dioxide
(pCO2)
pH
levels
that
sufficient
alter
activity
cognitive
function,
we
applied
a
recently
introduced
homeostatic
modeling
nutrients
waste
products
PET
data
acquired
young
older
adults
(Goyal
et
al.
Cell
Metab
26(2):353–360,
2017).
Our
results
demonstrate
reductions
CBF,
presence
virtually
unaltered
consumption
rates,
show
concurrent
increases
pCO2
associated
acid-shifts
possible
functional
relevance.
We
conclude
implications
altered
vascular
health
needs
be
revisited
light
its
central
removing
from
metabolism
at
resting
state
and,
future
studies,
during
external
stimulations.
Current Issues in Molecular Biology,
Journal Year:
2025,
Volume and Issue:
47(3), P. 189 - 189
Published: March 14, 2025
Multiple
lines
of
evidence
suggest
that
multiple
pathological
conditions
and
diseases
account
for
the
majority
human
mortality
are
driven
by
molecular
aging
process.
At
cellular
level,
can
largely
be
conceptualized
to
comprise
progressive
accumulation
damage,
leading
resultant
dysfunction.
As
many
diseases,
e.g.,
cancer,
coronary
heart
disease,
Chronic
obstructive
pulmonary
Type
II
diabetes
mellitus,
or
chronic
kidney
potentially
share
a
common
etiology,
then
identification
such
mechanisms
may
represent
an
ideal
locus
develop
targeted
prophylactic
agents
mitigate
this
disease-driving
mechanism.
Here,
using
input
artificial
intelligence
systems
generate
unbiased
disease
mechanism
profiles,
we
have
aimed
identify
key
signaling
new
disease-preventing
pathways
creation
chemical
interventions.
Using
combinatorial
informatics
approach,
identified
potential
critical
involving
recently
kinase,
Dual
specificity
tyrosine-phosphorylation-regulated
kinase
3
(DYRK3)
epidermal
growth
factor
receptor
(EGFR)
function
as
regulator
transition
health
into
via
control
fate
in
response
stressful
insults.
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(4), P. 585 - 585
Published: April 15, 2025
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
with
no
effective
treatments.
Hyperphosphorylation
of
tau
protein
contributes
to
neurodegeneration
in
AD.
Previous
studies
have
identified
pT231-tau
the
cis
conformation
as
an
early
driver
tauopathy
models.
Here,
we
identify
novel
neurotoxic
conformer
human
AD
neurons,
distinct
from
both
and
trans
conformations,
which
propose
gauche
conformer.
Notably,
levels
this
were
elevated
neurons
subjected
aging-associated
stress.
In
order
confirm
stress,
examined
p21
accumulation
iPSC-derived
mouse
cortical
under
aging
Targeted
elimination
mitigated
cultures.
These
findings
suggest
plays
key
role
tau-mediated
may
be
potential
therapeutic
target
for
