International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2440 - 2440
Опубликована: Март 9, 2025
The
blood–brain
barrier
(BBB)
is
essential
for
maintaining
brain
homeostasis
by
regulating
molecular
exchange
between
the
systemic
circulation
and
central
nervous
system.
However,
its
dysfunction,
often
driven
peripheral
inflammatory
processes,
has
been
increasingly
linked
to
development
progression
of
neurodegenerative
diseases
such
as
Alzheimer’s
Parkinson’s.
Emerging
evidence
suggests
that
gut–brain
axis
plays
a
key
role
in
BBB
integrity,
with
intestinal
dysbiosis
chronic
inflammation
contributing
disruption
through
immune
metabolic
pathways.
Furthermore,
selective
vulnerability
specific
regions
dysfunction
appears
be
influenced
regional
differences
vascularization,
activity,
permeability,
making
certain
areas
more
susceptible
processes.
This
review
explored
mechanisms
linking
inflammation,
gut
microbiota,
emphasizing
their
neurodegeneration.
A
comprehensive
literature
was
conducted
using
Web
Science,
PubMed,
Scopus,
Wiley,
ScienceDirect,
Medline,
covering
publications
from
2015
2025.
findings
highlight
complex
interplay
microbiota-derived
metabolites,
signaling,
underscoring
need
targeted
interventions
microbiome
modulation,
anti-inflammatory
therapies,
advanced
drug
delivery
systems.
heterogeneity
across
different
necessitates
region-specific
therapeutic
strategies.
Despite
advancements,
critical
knowledge
gaps
persist
regarding
precise
underlying
dysfunction.
Future
research
should
leverage
cutting-edge
methodologies
single-cell
transcriptomics
organ-on-chip
models
translate
preclinical
into
effective
clinical
applications.
Addressing
these
challenges
will
crucial
developing
personalized
approaches
mitigate
impact
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.
International Journal of Pharmaceutics,
Год журнала:
2025,
Номер
670, С. 125186 - 125186
Опубликована: Янв. 8, 2025
The
blood-brain
barrier
(BBB)
plays
a
vital
role
in
protecting
the
central
nervous
system
(CNS)
by
preventing
entry
of
harmful
pathogens
from
bloodstream.
However,
this
also
presents
significant
obstacle
when
it
comes
to
delivering
drugs
for
treatment
neurodegenerative
diseases
and
brain
cancer.
Recent
breakthroughs
nanotechnology
have
paved
way
creation
wide
range
nanoparticles
(NPs)
that
can
serve
as
carriers
diagnosis
therapy.
Regarding
their
promising
properties,
organic
NPs
potential
be
used
effective
drug
delivery
across
BBB
based
on
recent
advancements.
These
remarkable
ability
penetrate
using
various
mechanisms.
This
review
offers
comprehensive
examination
intricate
structure
distinct
properties
BBB,
emphasizing
its
crucial
function
preserving
balance
regulating
transport
ions
molecules.
disruption
conditions
such
stroke,
Alzheimer's
disease,
Parkinson's
disease
highlights
importance
developing
creative
approaches
drugs.
Through
encapsulation
therapeutic
molecules
precise
targeting
processes
vasculature,
NP
formulations
present
hopeful
strategy
improve
BBB.
We
explore
changes
pathological
investigate
factors
affect
successful
into
brain.
In
addition,
we
most
systems
associated
with
shown
positive
results
treating
ischemic
disorders.
opens
up
new
possibilities
nanotechnology-based
therapies
cerebral
diseases.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(3), С. 1914 - 1914
Опубликована: Фев. 5, 2024
Alzheimer’s
disease
(AD)
is
a
progressive
neurodegenerative
disorder
that
characterized
by
several
pathological
hallmarks,
including
the
deposition
of
amyloid-β
(Aβ)
plaques,
neurofibrillary
tangles,
blood–brain
barrier
(BBB)
dysfunction,
increased
oxidative
stress,
and
neuroinflammation.
Current
treatment
options
include
monoclonal
antibody
drugs,
acetylcholinesterase,
n-methyl-d-aspartate
(NMDA)
antagonists.
Although
those
treatments
provide
some
improvements
in
patients’
quality
life,
they
fail
to
prevent
or
cure
AD.
research
aims
identify
novel
targets
tools
for
AD
prevention
modification.
In
this
context,
studies
showed
beneficial
effect
Mediterranean
diet
One
integral
component
olive
oil
extra-virgin
(EVOO),
which
high
phenolic
compounds.
EVOO
other
olive-related
compounds
have
been
shown
reduce
risk
developing
mild
cognitive
impairment
(MCI)
review,
we
discuss
mechanisms
exert
neuroprotective
effects,
modulation
pathologies
promotion
health.
Findings
indicate
its
constituents
influence
key
processes
AD,
such
as
Aβ
aggregation,
tau
phosphorylation,
neuroinflammation,
while
also
enhancing
BBB
integrity
reducing
stress.
The
human
cited
reveal
consistent
trend
where
consumption
associated
with
benefits
decreased
related
dementias.
conclusion,
hold
promising
potential
representing
significant
shift
towards
more
effective
strategies
against
complex
disorder.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
13(21)
Опубликована: Март 2, 2024
Abstract
The
blood‐brain
barrier
(BBB)
is
a
highly
controlled
microenvironment
that
regulates
the
interactions
between
cerebral
blood
and
brain
tissue.
Due
to
its
selectivity,
many
therapeutics
targeting
various
neurological
disorders
are
not
able
penetrate
into
Pre‐clinical
studies
using
animals
other
in
vitro
platforms
have
shown
ability
fully
replicate
human
BBB
leading
failure
of
majority
clinical
trials.
However,
recent
innovations
ex
vivo
modeling
called
organs‐on‐chips
potential
create
more
accurate
disease
models
for
improved
drug
development.
These
microfluidic
induce
physiological
stressors
on
cultured
cells
generate
physiologically
BBBs
compared
previous
models.
In
this
review,
different
approaches
BBBs‐on‐chips
explored
alongside
their
application
therapeutic
efficacy.
Additionally,
use
delivery
discussed,
advances
linking
onto
multiorgan
mimic
organ
crosstalk
reviewed.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(1), С. 403 - 403
Опубликована: Янв. 5, 2025
The
Receptor
for
Advanced
Glycation
End
Products
(RAGE),
part
of
the
immunoglobulin
superfamily,
plays
a
significant
role
in
various
essential
functions
under
both
normal
and
pathological
conditions,
especially
progression
Alzheimer’s
disease
(AD).
RAGE
engages
with
several
damage-associated
molecular
patterns
(DAMPs),
including
advanced
glycation
end
products
(AGEs),
beta-amyloid
peptide
(Aβ),
high
mobility
group
box
1
(HMGB1),
S100
calcium-binding
proteins.
This
interaction
impairs
brain’s
ability
to
clear
Aβ,
resulting
increased
Aβ
accumulation,
neuronal
injury,
mitochondrial
dysfunction.
further
promotes
inflammatory
responses
oxidative
stress,
ultimately
leading
range
age-related
diseases.
Given
RAGE’s
AD,
inhibitors
that
target
its
ligands
hold
promise
as
new
strategies
treating
offering
possibilities
alleviating
this
serious
neurodegenerative
disease.
article
reviews
pathogenic
mechanisms
AD
summarizes
literature
on
between
AD-related
processes,
particular
focus
evidence
by
which
interactions
AGEs,
HMGB1,
proteins
induce
cognitive
impairment
AD.
Furthermore,
discusses
principles
action
targeting
RAGE-ligand
interactions,
along
relevant
clinical
trials.
Alzheimer s & Dementia,
Год журнала:
2025,
Номер
21(2)
Опубликована: Фев. 1, 2025
Abstract
INTRODUCTION
The
molecular
mechanisms
underlying
early‐onset
Alzheimer's
disease
(EOAD)
and
late‐onset
(LOAD)
remain
incompletely
understood,
particularly
in
Asian
populations.
METHODS
RNA‐sequencing
was
carried
out
on
blood
samples
from
248
participants
the
Seoul
National
University
Bundang
Hospital
cohort
to
perform
differential
gene
expression
(DGE)
weighted
co‐expression
network
analysis.
Findings
were
replicated
an
independent
Korean
(
N
=
275).
RESULTS
DGE
analysis
identified
18
88
dysregulated
genes
EOAD
LOAD,
respectively.
Network
a
LOAD‐associated
module
showing
significant
enrichment
pathways
related
mitophagy,
5′
adenosine
monophosphate‐activated
protein
kinase
signaling,
ubiquitin‐mediated
proteolysis.
In
replication
cohort,
downregulation
of
SMOX
PLVAP
LOAD
replicated,
highly
preserved.
addition,
associated
with
brain
amyloid
beta
deposition.
DISCUSSION
Our
findings
suggest
distinct
signatures
for
population,
providing
deeper
understanding
their
diagnostic
potential
mechanisms.
Highlights
Analysis
(LOAD),
Expression
levels
downregulated
LOAD.
Pathways
including
mitophagy
signaling
enriched
module.
A
preserved
across
two
cohorts.
Journal of Neuroimmunology,
Год журнала:
2024,
Номер
391, С. 578363 - 578363
Опубликована: Май 3, 2024
Neurological
diseases
with
a
neurodegenerative
component
have
been
associated
alterations
in
the
cerebrovasculature.
At
anatomical
level,
these
are
centred
around
changes
cerebral
blood
flow
and
vessel
organisation.
molecular
there
is
extensive
expression
of
cellular
adhesion
molecules
increased
release
pro-inflammatory
mediators.
Together,
has
found
to
negatively
impact
blood-brain
barrier
integrity.
Systemic
inflammation
accelerate
exacerbate
endothelial
dysfunction,
neuroinflammation
degeneration.
Here,
we
review
role
cerebrovasculature
dysfunction
disease
discuss
potential
contribution
intermittent
systemic
causing
pathology,
highlighting
possible
mechanism
that
may
allow
broad-spectrum
therapeutic
targeting
future.
Nutrients,
Год журнала:
2024,
Номер
16(14), С. 2244 - 2244
Опубликована: Июль 12, 2024
Aging
is
the
most
prominent
risk
factor
for
neurodegeneration
occurrence.
The
common
neurodegenerative
diseases
(NDs),
Alzheimer’s
(AD)
and
Parkinson’s
(PD)
diseases,
are
characterized
by
incidence
of
proteinopathy,
abnormal
activation
glial
cells,
oxidative
stress,
neuroinflammation,
impaired
autophagy
cellular
senescence
excessive
patient’s
age.
Moreover,
mitochondrial
disfunction,
epigenetic
alterations
neurogenesis
inhibition,
together
with
increased
blood–brain
barrier
permeability
gut
dysbiosis,
have
been
linked
to
ND
pathogenesis.
Since
NDs
still
lack
curative
treatment,
recent
research
has
sought
therapeutic
options
in
restoring
microbiota
supplementing
probiotic
bacteria-derived
metabolites
beneficial
action
host—so
called
postbiotics.
current
review
focuses
on
literature
explaining
mechanisms
involved
pathogenesis
addressing
impact
that
postbiotics
as
a
whole
mixture
particular
metabolites,
such
short-chain
fatty
acids
(SCFAs),
lactate,
polyamines,
polyphenols,
tryptophan
exopolysaccharides
bacterial
extracellular
vesicles,
ageing-associated
processes
underlying
also
discusses
issue
implementing
into
prophylaxis
therapy,
depicting
them
compounds
senescence-triggered
dysfunctions
worth
translating
from
bench
pharmaceutical
market
response
“silver
consumers”
demands.
