Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 10, 2025
Abstract
In
the
context
of
global
ageing,
prevalence
neurodegenerative
diseases
and
dementia,
such
as
Alzheimer’s
disease
(AD),
is
increasing.
However,
current
symptomatic
disease-modifying
therapies
have
achieved
limited
benefits
for
in
clinical
settings.
Halting
progress
neurodegeneration
cognitive
decline
or
even
improving
impaired
cognition
function
are
clinically
meaningful
goals
treatments
diseases.
Ageing
primary
risk
factor
their
associated
comorbidities,
vascular
pathologies,
elderly
individuals.
Thus,
we
aim
to
elucidate
role
ageing
from
perspective
a
complex
system,
which
brain
core
peripheral
organs
tissues
form
holistic
network
support
functions.
During
progressive
deterioration
structure
entire
body
hampers
its
active
adaptive
responses
various
stimuli,
thereby
rendering
individuals
more
vulnerable
Consequently,
propose
that
prevention
treatment
should
be
grounded
antiageing
rejuvenation
means
complemented
by
interventions
targeting
disease-specific
pathogenic
events.
This
integrated
approach
promising
strategy
effectively
prevent,
pause
slow
down
progression
Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Июнь 5, 2023
Abstract
Peripheral
inflammation,
defined
as
inflammation
that
occurs
outside
the
central
nervous
system,
is
an
age-related
phenomenon
has
been
identified
a
risk
factor
for
Alzheimer’s
disease.
While
role
of
chronic
peripheral
well
characterized
in
context
dementia
and
other
conditions,
less
known
about
neurologic
contribution
acute
inflammatory
insults
take
place
system.
Herein,
we
define
immune
challenge
form
pathogen
exposure
(e.g.,
viral
infection)
or
tissue
damage
surgery)
causes
large,
yet
time-limited,
response.
We
provide
overview
clinical
translational
research
examined
connection
between
disease,
focusing
on
three
categories
have
received
considerable
attention
recent
years:
infection,
critical
illness,
surgery.
Additionally,
review
neurobiological
mechanisms
which
facilitate
neural
response
to
discuss
potential
blood–brain
barrier
components
neuro-immune
axis
After
highlighting
knowledge
gaps
this
area
research,
propose
roadmap
address
methodological
challenges,
suboptimal
study
design,
paucity
transdisciplinary
efforts
thus
far
limited
our
understanding
how
pathogen-
damage-mediated
may
contribute
Finally,
therapeutic
approaches
designed
promote
resolution
be
used
following
preserve
brain
health
limit
progression
neurodegenerative
pathology.
Nature Medicine,
Год журнала:
2024,
Номер
30(10), С. 2777 - 2781
Опубликована: Июль 25, 2024
There
is
emerging
evidence
that
the
live
herpes
zoster
(shingles)
vaccine
might
protect
against
dementia.
However,
existing
data
are
limited
and
refer
only
to
vaccine,
which
now
discontinued
in
United
States
many
other
countries
favor
of
a
recombinant
vaccine.
Whether
shingles
protects
dementia
remains
unknown.
Here
we
used
natural
experiment
opportunity
created
by
rapid
transition
from
use
vaccines
compare
risk
between
types.
We
show
associated
with
significantly
lower
6
years
post-vaccination.
Specifically,
receiving
17%
increase
diagnosis-free
time,
translating
into
164
additional
days
lived
without
diagnosis
those
subsequently
affected.
The
was
also
risks
than
were
two
commonly
older
people:
influenza
tetanus-diphtheria-pertussis
vaccines.
effect
robust
across
multiple
secondary
analyses,
present
both
men
women
but
greater
women.
These
findings
should
stimulate
studies
investigating
mechanisms
underpinning
protection
could
facilitate
design
large-scale
randomized
control
trial
confirm
possible
benefit
Cell Reports,
Год журнала:
2025,
Номер
unknown, С. 115109 - 115109
Опубликована: Янв. 1, 2025
Alzheimer's
disease
(AD)
diagnosis
relies
on
the
presence
of
extracellular
β-amyloid
(Aβ)
and
intracellular
hyperphosphorylated
tau
(p-tau).
Emerging
evidence
suggests
a
potential
link
between
AD
pathologies
infectious
agents,
with
herpes
simplex
virus
1
(HSV-1)
being
leading
candidate.
Our
investigation,
using
metagenomics,
mass
spectrometry,
western
blotting,
decrowding
expansion
pathology,
detects
HSV-1-associated
proteins
in
human
brain
samples.
Expression
herpesvirus
protein
ICP27
increases
severity
strongly
colocalizes
p-tau
but
not
Aβ.
Modeling
organoids
shows
that
HSV-1
infection
elevates
phosphorylation.
Notably,
reduces
expression
markedly
decreases
post-infection
neuronal
death
from
64%
to
7%.
This
modeling
prompts
investigation
into
cGAS-STING-TBK1
pathway
products,
nuclear
factor
(NF)-κB
IRF-3,
which
AD.
Furthermore,
experimental
activation
STING
enhances
phosphorylation,
while
TBK1
inhibition
prevents
it.
Together,
these
findings
suggest
phosphorylation
acts
as
an
innate
immune
response
AD,
driven
by
cGAS-STING.
Abstract
Previous
studies
have
suggested
that
systemic
viral
infections
may
increase
risks
of
dementia.
Whether
this
holds
true
for
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
virus
is
unknown.
Determining
important
anticipating
the
potential
future
incidence
To
begin
to
do
this,
we
measured
plasma
biomarkers
linked
Alzheimer’s
disease
pathology
in
UK
Biobank
before
and
after
serology-confirmed
SARS-CoV-2
infections.
infection
was
associated
with
β-amyloid
pathology:
reduced
Aβ42:Aβ40
ratio
and,
more
vulnerable
participants,
lower
Aβ42
higher
pTau-181.
The
biomarker
changes
were
greater
participants
who
had
been
hospitalized
COVID-19
or
reported
hypertension
previously.
We
showed
brain
structural
imaging
patterns
disease,
cognitive
test
scores
poorer
overall
health
evaluations.
Our
data
from
post
hoc
case–control
matched
study
thus
provide
observational
evidence
can
be
older
adults.
While
these
results
not
establish
causality,
they
suggest
(and
possibly
other
inflammatory
diseases)
risk
disease.
