BioMolecular Concepts,
Год журнала:
2024,
Номер
15(1)
Опубликована: Янв. 1, 2024
Abstract
Alzheimer’s
disease
(AD)
is
characterized
by
immune
system
dysregulation,
impacting
both
central
and
peripheral
responses.
The
study
aimed
to
investigate
the
mechanism
behind
neurotoxic
effects
of
β-amyloid
(Aβ)
peptide
in
rat
brain
including
neuroinflammation,
neurodegeneration,
alterations
responses
(PIR).
neuroinflammation
brought
on
Aβ
1–42
unknown
influence
PIR.
Animal
models
were
prepared,
after
28
days,
control,
sham,
treated
rats
anaesthetized
inflammatory
markers
hippocampus
serum
levels
(reactive
oxygen
species,
nitrite,
tumor
necrosis
factor-α,
interleukin-1β),
some
PIR
(splenic
mononuclear
cells
or
MNC,
cytotoxicity
phagocytic
index
white
blood
leukocyte
adhesion
inhibition
LAI),
as
well
polymorphonuclear
spleen,
assessed.
In
addition
changes
responses,
present
found
that
AD
had
higher
markers.
Based
study,
irregularities
observed
regions
might
be
connected
which
facilitated
a
compromised
blood–brain
barrier.
Hence,
it
viable
propose
neuroinflammatory
condition
with
Aβ-induced
could
modify
areas
significantly
cytokines
hippocampal
tissue
Aβ-injected
rats.
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.
Abstract
Alzheimer’s
disease
(AD),
the
leading
cause
of
dementia,
is
characterized
by
accumulation
amyloid
plaques
and
neurofibrillary
tangles
in
brain.
This
condition
casts
a
significant
shadow
on
global
health
due
to
its
complex
multifactorial
nature.
In
addition
genetic
predispositions,
development
AD
influenced
myriad
risk
factors,
including
aging,
systemic
inflammation,
chronic
conditions,
lifestyle,
environmental
exposures.
Recent
advancements
understanding
pathophysiology
are
paving
way
for
enhanced
diagnostic
techniques,
improved
assessment,
potentially
effective
prevention
strategies.
These
discoveries
crucial
quest
unravel
complexities
AD,
offering
beacon
hope
management
treatment
options
millions
affected
this
debilitating
disease.
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Март 13, 2024
Abstract
Tissue-resident
macrophages
play
an
important
role
in
the
local
maintenance
of
homeostasis
and
immune
surveillance.
In
central
nervous
system
(CNS),
brain
are
anatomically
divided
into
parenchymal
microglia
non-parenchymal
border-associated
(BAMs).
Among
these
cell
populations,
have
been
well-studied
for
their
roles
during
development
as
well
health
disease.
BAMs,
mostly
located
choroid
plexus,
meningeal
perivascular
spaces,
now
gaining
increased
attention
due
to
advancements
multi-omics
technologies
genetic
methodologies.
Research
on
BAMs
over
past
decade
has
focused
ontogeny,
immunophenotypes,
involvement
various
CNS
diseases,
potential
therapeutic
targets.
Unlike
microglia,
display
mixed
origins
distinct
self-renewal
capacity.
believed
regulate
neuroimmune
responses
associated
with
barriers
contribute
immune-mediated
neuropathology.
Notably,
observed
function
diverse
cerebral
pathologies,
including
Alzheimer’s
disease,
Parkinson’s
multiple
sclerosis,
ischemic
stroke,
gliomas.
The
elucidation
heterogeneity
functions
neuroinflammation
is
mesmerizing,
since
it
may
shed
light
precision
medicine
that
emphasizes
deep
insights
programming
cues
unique
microenvironment.
this
review,
we
delve
latest
findings
covering
aspects
like
origins,
capacity,
adaptability,
implications
different
disorders.
Translational Neurodegeneration,
Год журнала:
2025,
Номер
14(1)
Опубликована: Янв. 27, 2025
Abstract
Alzheimer’s
disease
(AD)
is
the
most
common
type
of
dementia.
Monoclonal
antibodies
(MABs)
serve
as
a
promising
therapeutic
approach
for
AD
by
selectively
targeting
key
pathogenic
factors,
such
amyloid-β
(Aβ)
peptide,
tau
protein,
and
neuroinflammation.
Specifically,
based
on
their
efficacy
in
removing
Aβ
plaques
from
brains
patients
with
AD,
U.S.
Food
Drug
Administration
has
approved
three
anti-amyloid
MABs,
aducanumab
(Aduhelm®),
lecanemab
(Leqembi®),
donanemab
(Kisunla™).
Notably,
received
traditional
approval
after
demonstrating
clinical
benefit,
supporting
cascade
hypothesis.
These
MABs
are
categorized
affinity
to
diverse
conformational
features
Aβ,
including
monomer,
fibril,
protofibril,
plaque
forms
well
pyroglutamate
Aβ.
First-generation
non-toxic
monomeric
solanezumab,
bapineuzumab,
crenezumab,
failed
demonstrate
benefit
trials.
In
contrast,
second-generation
aducanumab,
lecanemab,
donanemab,
gantenerumab
directed
against
species
aggregates
have
shown
that
reducing
deposition
can
be
an
effective
strategy
slow
cognitive
impairment
AD.
this
review,
we
provide
comprehensive
overview
current
status,
mechanisms,
outcomes,
limitations
treatment
Moreover,
discuss
perspectives
future
directions
Frontiers in Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Фев. 16, 2024
Alzheimer's
disease
(AD)
is
a
prevalent
form
of
dementia
that
affects
an
estimated
32
million
individuals
globally.
Identifying
early
indicators
vital
for
screening
at-risk
populations
and
implementing
timely
interventions.
At
present,
there
urgent
need
sensitive
biomarkers
to
screen
at
risk
AD.
Among
all
sensory
biomarkers,
olfaction
currently
one
the
most
promising
Olfactory
dysfunction
signifies
decline
in
ability
detect,
identify,
or
remember
odors.
Within
spectrum
AD,
impairment
olfactory
identification
precedes
detectable
cognitive
impairments,
including
mild
(MCI)
even
stage
subjective
(SCD),
by
several
years.
closely
linked
clinical
symptoms
neuropathological
accompanied
significant
structural
functional
abnormalities
brain.
behavior
examination
can
subjectively
evaluate
abilities
identification,
threshold,
discrimination.
magnetic
resonance
imaging
(fMRI)
provide
relatively
objective
assessment
capabilities,
with
potential
become
tool
exploring
neural
mechanisms
damage
Here,
we
review
recent
literature
on
characteristics,
neuropathology,
AD
continuum.
We
focus
changes
detected
behavioral
fMRI
assessments
discuss
these
techniques
MCI
preclinical
Despite
challenges
limitations
existing
research,
has
demonstrated
its
value
assessing
neurodegenerative
diseases
may
serve
as
indicator
future.
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Апрель 16, 2024
Abstract
Trillions
of
intestinal
bacteria
in
the
human
body
undergo
dynamic
transformations
response
to
physiological
and
pathological
changes.
Alterations
their
composition
metabolites
collectively
contribute
progression
Alzheimer’s
disease.
The
role
gut
microbiota
disease
is
diverse
complex,
evidence
suggests
lipid
metabolism
may
be
one
potential
pathways.
However,
mechanisms
that
mediate
pathology
remain
unclear,
necessitating
further
investigation
for
clarification.
This
review
highlights
current
understanding
how
disrupts
discusses
implications
these
discoveries
guiding
strategies
prevention
or
treatment
based
on
existing
data.
