Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Ноя. 13, 2023
Alzheimer’s
disease
(AD)
is
a
common
neurodegenerative
disorder
characterized
by
the
accumulation
of
amyloid-beta
(Aβ),
hyperphosphorylation
tau,
and
neuroinflammation
in
brain.
The
blood–brain
barrier
(BBB)
limits
solutes
from
circulating
blood
entering
brain,
which
essential
for
neuronal
functioning.
Focusing
on
BBB
function
important
early
detection
AD
in-depth
study
pathogenic
mechanisms.
However,
mechanism
alteration
still
unclear,
hinders
further
research
therapeutics
that
target
to
delay
progression
AD.
exact
timing
vascular
abnormalities
complex
cause-and-effect
relationships
remain
uncertain.
Thus,
it
necessary
summarize
emphasize
this
process.
First,
review,
current
evidence
dysfunction
summarized.
Then,
interrelationships
mechanisms
between
risk
factors
AD,
such
as
Aβ,
neuroinflammation,
apolipoprotein
E
(ApoE)
genotype
aging,
were
analyzed.
Finally,
we
discuss
status
future
directions
therapeutic
strategies
targeting
BBB.
We
hope
these
summaries
or
reviews
will
allow
readers
better
understand
relationship
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(17), С. 9583 - 9583
Опубликована: Авг. 24, 2022
The
glucagon-like
peptide-1
(GLP-1)
is
a
pleiotropic
hormone
well
known
for
its
incretin
effect
in
the
glucose-dependent
stimulation
of
insulin
secretion.
However,
GLP-1
also
produced
brain
and
displays
critical
role
neuroprotection
inflammation
by
activating
receptor
signaling
pathways.
Several
studies
vivo
vitro
using
preclinical
models
neurodegenerative
diseases
show
that
GLP-1R
activation
has
anti-inflammatory
properties.
This
review
explores
molecular
mechanistic
action
RAS
relation
to
brain.
These
findings
update
our
knowledge
potential
benefits
GLP-1RAS
actions
reducing
inflammatory
response.
molecules
emerge
as
therapeutic
tool
treating
neuroinflammatory
pathologies.
Physiological Reviews,
Год журнала:
2022,
Номер
103(1), С. 649 - 716
Опубликована: Сен. 1, 2022
Somatic
mosaicism,
the
occurrence
of
multiple
genetically
distinct
cell
clones
within
same
tissue,
is
an
evitable
consequence
human
aging.
The
hematopoietic
system
no
exception
to
this,
where
studies
have
revealed
presence
expanded
blood
carrying
mutations
in
preleukemic
driver
genes
and/or
genetic
alterations
chromosomes.
This
phenomenon
referred
as
clonal
hematopoiesis
and
remarkably
prevalent
elderly
individuals.
While
represents
early
step
toward
a
hematological
malignancy,
most
individuals
will
never
develop
cancer.
Somewhat
unexpectedly,
epidemiological
found
that
associated
with
increase
risk
all-cause
mortality
age-related
disease,
particularly
cardiovascular
system.
Studies
using
murine
models
begun
shed
light
on
this
relationship,
suggesting
mature
cells
can
causally
contribute
aging
disease
by
augmenting
inflammatory
processes.
Here
we
provide
up-to-date
review
context
somatic
mosaicism
describe
recent
reported
associations
disease.
We
also
discuss
experimental
provided
important
mechanistic
insight
into
how
promote
knowledge
could
be
leveraged
treat
hematopoiesis.
Frontiers in Aging Neuroscience,
Год журнала:
2022,
Номер
14
Опубликована: Май 19, 2022
Various
age-related
diseases
involve
systemic
inflammation,
i.e.
a
stereotyped
series
of
acute
immune
system
responses,
and
aging
itself
is
commonly
associated
with
low-grade
inflammation
or
inflamm’aging.
Neuroinflammation
defined
as
inflammation-like
processes
inside
the
central
nervous
system,
which
this
review
discusses
possible
link
between
cardiovascular
disease-related
chronic
neurodegenerative
diseases.
To
aim,
neuroinflammation
mechanisms
are
first
summarized,
encompassing
cellular
effectors
molecular
mediators.
A
comparative
survey
best-known
physiological
contexts
(neurodegenerative
transient
ischemia)
reveals
some
common
features
such
microglia
activation.
The
recently
published
transcriptomic
characterizations
have
pointed
marker
core
signature
among
diseases,
but
also
unraveled
discrepancies
neuroinflammations
related
vascular
origin.
We
next
links
neuroinflammation,
beginning
respective
pro-inflammatory
cells,
macrophages
microglia.
Finally,
we
point
out
gap
knowledge
concerning
atherosclerosis-related
for
most
surprising
given
that
atherosclerosis
established
major
risk
factor
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Дек. 8, 2022
Background
Using
interpretable
machine
learning,
we
sought
to
define
the
immune
microenvironment
subtypes
and
distinctive
genes
in
AD.
Methods
ssGSEA,
LASSO
regression,
WGCNA
algorithms
were
used
evaluate
state
AD
patients.
To
predict
fate
of
identify
genes,
six
learning
developed.
The
output
models
was
interpreted
using
SHAP
LIME
algorithms.
For
external
validation,
four
separate
GEO
databases
used.
We
estimated
subgroups
immunological
unsupervised
clustering.
Further
research
done
on
variations
microenvironment,
enhanced
functions
pathways,
therapeutic
medicines
between
these
subtypes.
Finally,
expression
characteristic
verified
AlzData
pan-cancer
RT-PCR
analysis.
Results
It
determined
that
is
connected
changes
microenvironment.
revealed
31
potential
which
greenyellow
blue
modules
shown
be
most
associated
with
infiltrated
cells.
In
testing
set,
XGBoost
algorithm
had
best
performance
an
AUC
0.86
a
P-R
value
0.83.
Following
screening
set
by
verification
independent
datasets,
five
(CXCR4,
PPP3R1,
HSP90AB1,
CXCL10,
S100A12)
closely
pathological
biomarkers
allowed
for
accurate
prediction
progression
found
microenvironment-related
genes.
feature
gene-based
nomogram
may
provide
clinical
advantages
Two
patients
identified,
subtype2
linked
metabolic
phenotype,
subtype1
belonged
immune-active
kind.
MK-866
arachidonyltrifluoromethane
identified
as
top
treatment
agents
1
2,
respectively.
These
distinguishing
intimately
development
disease,
according
Alzdata
database,
research,
Conclusion
hub
are
strongly
pathology
CXCR4,
S100A12.
hypothesized
molecular
might
offer
novel
perceptions
individualized
treatment.
Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Ноя. 13, 2023
Alzheimer’s
disease
(AD)
is
a
common
neurodegenerative
disorder
characterized
by
the
accumulation
of
amyloid-beta
(Aβ),
hyperphosphorylation
tau,
and
neuroinflammation
in
brain.
The
blood–brain
barrier
(BBB)
limits
solutes
from
circulating
blood
entering
brain,
which
essential
for
neuronal
functioning.
Focusing
on
BBB
function
important
early
detection
AD
in-depth
study
pathogenic
mechanisms.
However,
mechanism
alteration
still
unclear,
hinders
further
research
therapeutics
that
target
to
delay
progression
AD.
exact
timing
vascular
abnormalities
complex
cause-and-effect
relationships
remain
uncertain.
Thus,
it
necessary
summarize
emphasize
this
process.
First,
review,
current
evidence
dysfunction
summarized.
Then,
interrelationships
mechanisms
between
risk
factors
AD,
such
as
Aβ,
neuroinflammation,
apolipoprotein
E
(ApoE)
genotype
aging,
were
analyzed.
Finally,
we
discuss
status
future
directions
therapeutic
strategies
targeting
BBB.
We
hope
these
summaries
or
reviews
will
allow
readers
better
understand
relationship
