Alzheimer's
disease
(AD)
is
one
of
the
most
common
forms
dementia
in
elderly,
characterized
by
progressive
neurodegeneration.
While
exact
etiology
AD
remains
unclear,
immune
inflammation
known
to
play
a
significant
role
disease.
This
study
utilized
two-sample
Mendelian
randomization
(MR)
approach
assess
causal
relationship
between
different
types
cells
and
AD,
while
considering
inflammatory
factors
as
intermediate
variables.
Data
were
collected
from
three
sources:
cell
data
(731
phenotypes),
(48
cytokines
8,293
individuals),
(35,274
cases,
59,163
controls).
Multiple
MR
methods
employed
minimize
bias,
detailed
descriptions
instrumental
variable
selection
statistical
provided.
The
findings
suggest
potential
relationships
six
well
13
factors.
Additionally,
two
statistically
found
have
with
AD.
Specifically,
CD33-HLA
DR
+
CD45
on
may
further
influence
regulating
Interleukin-2
levels.
provides
valuable
insights
into
immunoinflammatory
pathogenesis
offers
partial
guidance
for
development
relevant
interventions,
thereby
contributing
beneficial
information
prevention
treatment
related
diseases.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Авг. 23, 2024
Abstract
Alzheimer’s
disease
(AD)
stands
as
the
predominant
form
of
dementia,
presenting
significant
and
escalating
global
challenges.
Its
etiology
is
intricate
diverse,
stemming
from
a
combination
factors
such
aging,
genetics,
environment.
Our
current
understanding
AD
pathologies
involves
various
hypotheses,
cholinergic,
amyloid,
tau
protein,
inflammatory,
oxidative
stress,
metal
ion,
glutamate
excitotoxicity,
microbiota-gut-brain
axis,
abnormal
autophagy.
Nonetheless,
unraveling
interplay
among
these
pathological
aspects
pinpointing
primary
initiators
require
further
elucidation
validation.
In
past
decades,
most
clinical
drugs
have
been
discontinued
due
to
limited
effectiveness
or
adverse
effects.
Presently,
available
primarily
offer
symptomatic
relief
often
accompanied
by
undesirable
side
However,
recent
approvals
aducanumab
(
1
)
lecanemab
2
Food
Drug
Administration
(FDA)
present
potential
in
disrease-modifying
Nevertheless,
long-term
efficacy
safety
need
Consequently,
quest
for
safer
more
effective
persists
formidable
pressing
task.
This
review
discusses
pathogenesis,
advances
diagnostic
biomarkers,
latest
updates
trials,
emerging
technologies
drug
development.
We
highlight
progress
discovery
selective
inhibitors,
dual-target
allosteric
modulators,
covalent
proteolysis-targeting
chimeras
(PROTACs),
protein-protein
interaction
(PPI)
modulators.
goal
provide
insights
into
prospective
development
application
novel
drugs.
Molecular Biomedicine,
Год журнала:
2023,
Номер
4(1)
Опубликована: Ноя. 8, 2023
Abstract
The
Janus
kinase-signal
transducer
and
transcription
activator
pathway
(JAK-STAT)
serves
as
a
cornerstone
in
cellular
signaling,
regulating
physiological
pathological
processes
such
inflammation
stress.
Dysregulation
this
can
lead
to
severe
immunodeficiencies
malignancies,
its
role
extends
neurotransduction
pro-inflammatory
signaling
mechanisms.
Although
JAK
inhibitors
(Jakinibs)
have
successfully
treated
immunological
inflammatory
disorders,
their
application
has
generally
been
limited
diseases
with
similar
pathogenic
features.
Despite
the
modest
expression
of
JAK-STAT
CNS,
it
is
crucial
for
functions
cortex,
hippocampus,
cerebellum,
making
relevant
conditions
like
Parkinson's
disease
other
neuroinflammatory
disorders.
Furthermore,
influence
on
serotonin
receptors
phospholipase
C
implications
stress
mood
This
review
expands
understanding
JAK-STAT,
moving
beyond
traditional
contexts
explore
stress-related
disorders
CNS
function.
Recent
findings,
effectiveness
Jakinibs
chronic
rheumatoid
arthritis,
expand
therapeutic
applicability.
Advances
isoform-specific
inhibitors,
including
filgotinib
upadacitinib,
promise
greater
specificity
fewer
off-target
effects.
Combination
therapies,
involving
monoclonal
antibodies,
aiming
enhance
efficacy
also
give
great
hope.
Overall,
bridges
gap
between
basic
science
clinical
application,
elucidating
complex
human
health
guiding
future
interventions.
Graphical
Cells,
Год журнала:
2024,
Номер
13(6), С. 511 - 511
Опубликована: Март 14, 2024
Neuroinflammatory
and
neurodegenerative
disorders
including
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
traumatic
brain
injury
(TBI)
Amyotrophic
lateral
sclerosis
(ALS)
are
chronic
major
health
disorders.
The
exact
mechanism
of
the
neuroimmune
dysfunctions
these
pathogeneses
is
currently
not
clearly
understood.
These
show
dysregulated
inflammatory
responses,
activation
neurons,
glial
cells,
neurovascular
unit
damage
associated
with
excessive
release
proinflammatory
cytokines,
chemokines,
neurotoxic
mediators,
infiltration
peripheral
immune
cells
into
brain,
as
well
entry
mediators
through
damaged
endothelial
blood–brain
barrier
tight
junction
proteins.
Activation
leads
to
many
molecules
that
cause
neuroinflammation
neurodegeneration.
Gulf
War
Illness
(GWI)
myalgic
encephalomyelitis/chronic
fatigue
syndrome
(ME/CFS)
also
dysfunctions.
Currently,
there
no
effective
disease-modifying
therapeutic
options
available
for
diseases.
Human
induced
pluripotent
stem
cell
(iPSC)-derived
astrocytes,
microglia,
pericytes
used
models
drug
discovery.
This
review
highlights
certain
recent
trends
in
neuroinflammatory
responses
iPSC-derived
applications
Neurobiology of Disease,
Год журнала:
2024,
Номер
192, С. 106426 - 106426
Опубликована: Фев. 6, 2024
The
term
"glymphatic"
emerged
roughly
a
decade
ago,
marking
pivotal
point
in
neuroscience
research.
glymphatic
system,
glial-dependent
perivascular
network
distributed
throughout
the
brain,
has
since
become
focal
of
investigation.
There
is
increasing
evidence
suggesting
that
impairment
system
appears
to
be
common
feature
neurodegenerative
disorders,
and
this
exacerbates
as
disease
progression.
Nevertheless,
factors
contributing
dysfunction
across
most
disorders
remain
unclear.
Inflammation,
however,
suspected
play
role.
Dysfunction
can
lead
significant
accumulation
protein
waste
products,
which
trigger
inflammation.
interaction
between
inflammation
cyclical
potentially
synergistic.
Yet,
current
research
limited,
there
lack
comprehensive
models
explaining
association.
In
perspective
review,
we
propose
novel
model
inflammation,
impaired
function,
interconnected
vicious
cycle.
By
presenting
experimental
from
existing
literature,
aim
demonstrate
that:
(1)
aggravates
dysfunction,
(2)
exacerbated
progression,
(3)
progression
promotes
Finally,
implication
proposed
discussed.
