Alzheimer s Research & Therapy,
Год журнала:
2020,
Номер
12(1)
Опубликована: Апрель 21, 2020
Abstract
Background
Chronic
neuroinflammation,
aggressive
amyloid
beta
(Aβ)
deposition,
neuronal
cell
loss,
and
cognitive
impairment
are
pathological
presentations
of
Alzheimer’s
disease
(AD).
Therefore,
resolution
neuroinflammation
inhibition
Aβ-driven
pathology
have
been
suggested
to
be
important
strategies
for
AD
therapy.
Previous
efforts
prevent
progression
identified
p38
mitogen-activated
protein
kinases
(MAPKs)
as
a
promising
target
Recent
studies
showed
pharmacological
p38α
MAPK
improved
memory
in
mouse
models.
Methods
In
this
study,
we
used
an
model,
5XFAD,
explore
the
therapeutic
potential
NJK14047
which
is
novel,
selective
p38α/β
inhibitor.
The
mice
were
injected
with
2.5
mg/kg
or
vehicle
every
other
day
3
months.
Morris
water
maze
task
histological
imaging
analysis
performed.
Protein
mRNA
expression
levels
measured
using
immunoblotting
qRT-PCR,
respectively.
vitro
conducted
measure
cytotoxicity
microglia-
astrocyte-conditioned
medium
on
primary
neurons
MTT
assay
TUNEL
assay.
Results
treatment
downregulated
phospho-p38
levels,
decreased
amount
Aβ
deposits,
reduced
spatial
learning
loss
9-month-old
5XFAD
mice.
While
pro-inflammatory
conditions
decreased,
alternatively
activated
microglial
markers
phagocytic
receptors
was
increased.
Furthermore,
number
degenerating
labeled
Fluoro-Jade
B
brains
neuroprotective
effect
further
confirmed
by
studies.
Conclusion
Taken
together,
inhibitor
successfully
effects
Based
our
data,
strategy
therapy,
suggesting
one
candidates
therapeutics
targeting
MAPKs.
Genes,
Год журнала:
2019,
Номер
10(2), С. 117 - 117
Опубликована: Фев. 5, 2019
Nm
(2′-O-methylation)
is
one
of
the
most
common
modifications
in
RNA
world.
It
has
potential
to
influence
molecules
multiple
ways,
such
as
structure,
stability,
and
interactions,
play
a
role
various
cellular
processes
from
epigenetic
gene
regulation,
through
translation
self
versus
non-self
recognition.
Yet,
building
scientific
knowledge
on
matter
been
hampered
for
long
time
by
challenges
detecting
mapping
this
modification.
Today,
with
latest
advancements
area,
more
sites
are
discovered
RNAs
(tRNA,
rRNA,
mRNA,
small
non-coding
RNA)
linked
normal
or
pathological
conditions.
This
review
aims
synthesize
Nm-associated
human
diseases
known
date
tackle
indirect
links
some
other
biological
defects.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(7), С. 6518 - 6518
Опубликована: Март 30, 2023
Alzheimer’s
disease
is
one
of
the
most
commonly
diagnosed
cases
senile
dementia
in
world.
It
an
incurable
process,
often
leading
to
death.
This
multifactorial,
and
factor
this
inflammation.
Numerous
mediators
secreted
by
inflammatory
cells
can
cause
neuronal
degeneration.
Neuritis
may
coexist
with
other
mechanisms
disease,
contributing
progression,
also
directly
underlie
AD.
Although
much
has
been
established
about
processes
pathogenesis
AD,
many
aspects
remain
unexplained.
The
work
devoted
particular
pathomechanism
inflammation
its
role
diagnosis
treatment.
An
in-depth
detailed
understanding
neuroinflammation
help
development
diagnostic
methods
for
early
contribute
new
therapeutic
strategies
disease.
Alzheimer s & Dementia,
Год журнала:
2021,
Номер
17(5), С. 768 - 776
Опубликована: Янв. 6, 2021
Abstract
Introduction
We
investigate
dementia
risk
in
older
adults
with
different
disease
patterns
and
explore
the
role
of
inflammation
apolipoprotein
E
(
APOE
)
genotype.
Methods
A
total
2,478
dementia‐free
participants
two
or
more
chronic
diseases
(ie,
multimorbidity)
part
Swedish
National
study
on
Aging
Care
Kungsholmen
(SNAC‐K)
were
grouped
according
to
their
multimorbidity
followed
detect
clinical
dementia.
The
potential
modifier
effect
C‐reactive
protein
(CRP)
genotype
was
tested
through
stratified
analyses.
Results
People
neuropsychiatric
,
cardiovascular
sensory
impairment/cancer
had
increased
hazards
for
compared
unspecific
(Hazard
ration
(HR)
1.66,
95%
confidence
interval
[CI]
1.13‐2.42;
1.61,
CI
1.17‐2.29;
1.32,
1.10‐1.71,
respectively).
Despite
lack
statistically
significant
interaction,
high
CRP
within
these
patterns,
being
ε4
carriers
heightened
multimorbidity.
Discussion
Individuals
neuropsychiatric,
cardiovascular,
are
at
ε4,
may
further
increase
risk.
Identifying
such
high‐risk
groups
might
allow
tailored
interventions
prevention.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(2), С. 616 - 616
Опубликована: Янв. 6, 2022
Dementia
is
a
neurodegenerative
condition
that
considered
major
factor
contributing
to
cognitive
decline
reduces
independent
function.
Pathophysiological
pathways
are
not
well
defined
for
diseases
such
as
dementia;
however,
published
evidence
has
shown
the
role
of
numerous
inflammatory
processes
in
brain
toward
their
pathology.
Microglia
central
nervous
system
(CNS)
principal
components
brain’s
immune
defence
and
can
detect
harmful
or
external
pathogens.
When
stimulated,
cells
trigger
neuroinflammatory
responses
by
releasing
proinflammatory
chemokines,
cytokines,
reactive
oxygen
species,
nitrogen
species
order
preserve
cell’s
microenvironment.
These
markers
include
cytokines
IL-1,
IL-6,
TNFα
chemokines
CCR3
CCL2
CCR5.
Microglial
may
produce
prolonged
response
that,
some
circumstances,
indicated
promotion
diseases.
The
present
review
focused
on
involvement
microglial
cell
activation
throughout
conditions
link
between
dementia.
Journal of Neuroinflammation,
Год журнала:
2022,
Номер
19(1)
Опубликована: Сен. 8, 2022
Multifactorial
diseases
are
characterized
by
inter-individual
variation
in
etiology,
age
of
onset,
and
penetrance.
These
tend
to
be
relatively
common
arise
from
the
combined
action
genetic
environmental
factors;
however,
parsing
convoluted
mechanisms
underlying
these
gene-by-environment
interactions
presents
a
significant
challenge
their
study
management.
For
neurodegenerative
disorders,
resolving
this
is
imperative,
given
enormous
health
societal
burdens
they
impose.
The
which
effects
may
act
concert
destabilize
homeostasis
elevate
risk
has
become
major
research
focus
disease.
Emphasis
further
being
placed
on
determining
extent
unifying
biological
principle
account
for
progressively
diminishing
capacity
system
buffer
disease
phenotypes,
as
increases.
Data
emerging
studies
common,
providing
insights
pragmatically
connect
that
previously
seemed
disparate.
In
review,
we
discuss
evidence
positing
inflammation
homeostatic
destabilization
affecting
risk,
progression
diseases.
Specifically,
how
associated
with
Alzheimer
Parkinson
contribute
pro-inflammatory
responses,
such
predisposition
exacerbated
insults,
theme
leveraged
ongoing
search
effective
therapeutic
interventions.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(22), С. 16288 - 16288
Опубликована: Ноя. 14, 2023
The
blood-brain
barrier
(BBB)
is
a
unique
and
selective
feature
of
the
central
nervous
system's
vasculature.
BBB
dysfunction
has
been
observed
as
an
early
sign
Alzheimer's
Disease
(AD)
before
onset
dementia
or
neurodegeneration.
intricate
relationship
between
pathogenesis
AD,
especially
in
context
neurovascular
coupling
overlap
pathophysiology
neurodegenerative
cerebrovascular
diseases,
underscores
urgency
to
understand
BBB's
role
more
deeply.
Preserving
restoring
function
emerges
potentially
promising
strategy
for
mitigating
progression
severity
AD.
Molecular
genetic
changes,
such
isoform
ε4
apolipoprotein
E
(ApoEε4),
significant
risk
factor
promoter
dysfunction,
have
shown
mediate
disruption.
Additionally,
receptors
transporters
like
low-density
lipoprotein
receptor-related
protein
1
(LRP1),
P-glycoprotein
(P-gp),
receptor
advanced
glycation
end
products
(RAGEs)
implicated
AD's
pathogenesis.
In
this
comprehensive
review,
we
endeavor
shed
light
on
pathogenic
therapeutic
connections
AD
BBB.
We
also
delve
into
latest
developments
pioneering
strategies
targeting
interventions,
addressing
its
potential
carrier.
By
providing
integrative
perspective,
anticipate
paving
way
future
research
treatments
focused
exploiting
therapy.
Frontiers in Neuroscience,
Год журнала:
2019,
Номер
13
Опубликована: Фев. 4, 2019
Alzheimer's
disease
(AD)
is
a
devastating
neurological
condition
associated
with
abnormal
protein
modification,
inflammation
and
memory
impairment.
Aggregated
amyloid
beta
(Aβ)
phosphorylated
tau
proteins
are
medical
diagnostic
features
but
detected
only
after
the
has
progressed
to
advanced
stages.
The
loss
of
in
AD
been
central
cholinergic
dysfunction
basal
forebrain,
where
circuitry
projects
cerebral
cortex
hippocampus.
Current
medications
target
acetylcholine
metabolism
stabilize
decline.
Various
reports
link
progression
declining
activity
forebrain
neurons.
neurotrophin,
nerve
growth
factor
(NGF),
enhances
survival
effects
neurons,
which
retrogradely
transported
from
hippocampus
forebrain.
Recent
studies
have
shown
that
NGF
plays
role
aging
as
well
age-related
diseases
such
AD,
since
can
interact
pre-existing
abnormalities
trophic
signalling
trigger
cognitive
decline
observed
AD.
Further,
gradual
dysregulation
neurotrophic
factors
brain
derived
(BDNF)
during
development
thus
intensifying
further
research
targeting
these
modifying
therapies
against
Today,
there
no
cure
available
for
symptomatic
treatment
like
cholinesterase
inhibitors
(ChEIs)
memantine
transient
moderate.
Although
many
carried
out,
yet
breakthrough
new
highly
needed.
Therefore
need
review
advancements
its
potential
therapeutic
implications
In
this
review,
we
will
put
emphasis
on
focus
encapsulated
biodelivery
(ECB)
therapy
method
summary,
hope
describe
experimental
clinical
data,
demonstrating
important
roles
treatment,
an
efficient
