Journal of Nanobiotechnology,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: April 1, 2025
Extracellular
particles
(EPs),
including
extracellular
vesicles
(EVs)
and
non-vesicular
(NVEPs),
are
multimolecular
biomaterials
released
by
cells
that
play
a
crucial
role
in
intercellular
communication.
Recently,
new
subtypes
of
EPs
associated
with
central
nervous
system
(CNS),
such
as
exophers
supermeres
have
been
identified.
These
provide
perspectives
for
understanding
the
pathological
progression
CNS
disorders
confer
potential
diagnostic
value
liquid
biopsies
neurodegenerative
diseases
(NDs).
Moreover,
emerged
promising
drug
delivery
vehicles
targeted
platforms
CNS-specific
therapies.
In
this
review,
we
delineate
landscape
EP
their
roles
pathophysiology
diseases.
We
also
review
recent
advances
EP-based
diagnosis
NDs
highlight
importance
analytical
single-particle
resolution
exploitation
biomarkers.
Furthermore,
summarize
application
engineered
EVs
treatment
outline
underexplored
NVEPs
novel
therapeutic
agents.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(12), P. 10021 - 10021
Published: June 12, 2023
As
an
iron-dependent
regulated
form
of
cell
death,
ferroptosis
is
characterized
by
lipid
peroxidation
and
has
been
implicated
in
the
occurrence
development
various
diseases,
including
nervous
system
diseases
injuries.
Ferroptosis
become
a
potential
target
for
intervention
these
or
injuries
relevant
preclinical
models.
member
Acyl-CoA
synthetase
long-chain
family
(ACSLs)
that
can
convert
saturated
unsaturated
fatty
acids,
Acyl—CoA
familymember4
(ACSL4)
involved
regulation
arachidonic
acid
eicosapentaenoic
acid,
thus
leading
to
ferroptosis.
The
underlying
molecular
mechanisms
ACSL4-mediated
will
promote
additional
treatment
strategies
injury
conditions.
Our
review
article
provides
current
view
ferroptosis,
mainly
structure
function
ACSL4,
as
well
role
ACSL4
We
also
summarize
latest
research
progress
central
further
proving
ACSL4-medicated
important
Acta Neuropathologica,
Journal Year:
2024,
Volume and Issue:
147(1)
Published: Jan. 19, 2024
Abstract
The
development
of
in
vitro
seed
amplification
assays
(SAA)
detecting
misfolded
alpha-synuclein
(αSyn)
cerebrospinal
fluid
(CSF)
and
other
tissues
has
provided
a
pathology-specific
biomarker
for
Lewy
body
disease
(LBD).
However,
αSyn
SAA
diagnostic
performance
early
pathological
stages
or
low
(LB)
pathology
load
only
been
assessed
small
cohorts.
Moreover,
the
relationship
between
kinetic
parameters,
number
brain
seeds
LB
burden
by
immunohistochemistry
never
systematically
investigated.
We
tested
269
antemortem
CSF
samples
138
serially
diluted
homogenates
from
patients
with
without
neuropathological
evidence
LBD
different
Real-Time
Quaking-Induced
Conversion
(RT-QuIC)
SAA.
we
looked
consecutive
series
604
Creutzfeldt–Jakob
(CJD)-affected
brains.
RT-QuIC
showed
100%
sensitivity
limbic
neocortical
stages.
assay
was
significantly
lower
(37.5%
Braak
1
2,
73.3%
3)
focal
(50%
amygdala-predominant).
average
positive
replicates
correlated
stage.
Brain
homogenate
higher
than
detection
αSyn.
In
latter,
parameter
lag
phase
(time
to
reach
threshold)
strongly
concentration
serial
dilution
experiments.
Finally,
incidental
prevalence
8%
CJD
cohort.
present
results
indicate
that
(a)
high
specificity
sufficient
detect
all
at
>
3
most
those
stage
3;
(b)
deposition
precedes
formation
neurites;
(c)
provides
“quantitative”
information
regarding
burden,
being
promising
variables
be
used
clinical
setting.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(4), P. 2009 - 2009
Published: Feb. 7, 2024
The
core
pathological
event
in
Parkinson’s
disease
(PD)
is
the
specific
dying
of
dopamine
(DA)
neurons
substantia
nigra
pars
compacta
(SNc).
reasons
why
SNc
DA
are
especially
vulnerable
and
idiopathic
PD
has
only
been
found
humans
still
puzzling.
two
main
underlying
factors
neuron
vulnerability
appear
related
to
high
production,
namely
(i)
toxic
effects
cytoplasmic
metabolism
(ii)
continuous
cytosolic
Ca2+
oscillations
absence
Ca2+-buffer
protein
calbindin.
Both
cause
oxidative
stress
by
producing
highly
reactive
quinones
increasing
intra-mitochondrial
concentrations,
respectively.
High
expression
human
cell
bodies
suggested
abundant
presence
DA-derived
pigment
neuromelanin,
which
not
such
abundance
other
species
associated
with
toxicity
at
higher
levels.
created
their
production
system,
despite
fact
that
SN
does
use
unusually
amounts
energy,
explains
sensitive
various
genetic
environmental
create
mitochondrial
damage
thereby
promote
PD.
Aging
increases
multiple
risk
for
PD,
and,
a
large
extent,
accelerated
aging.
To
prevent
neurodegeneration,
possible
approaches
discussed
here
(1)
reducing
accumulation,
(2)
blocking
oscillations,
(3)
providing
bioenergetic
support.
Life,
Journal Year:
2024,
Volume and Issue:
14(10), P. 1234 - 1234
Published: Sept. 26, 2024
Microbes
have
inhabited
the
earth
for
hundreds
of
millions
years
longer
than
humans.
The
microbiota-gut-brain
axis
(MGBA)
represents
a
bidirectional
communication
pathway.
These
communications
occur
between
central
nervous
system
(CNS),
enteric
(ENS),
and
emotional
cognitive
centres
brain.
field
research
on
gut-brain
has
grown
significantly
during
past
two
decades.
Signalling
occurs
gut
microbiota
brain
through
neural,
endocrine,
immune,
humoral
pathways.
A
substantial
body
evidence
indicates
that
MGBA
plays
pivotal
role
in
various
neurological
diseases.
include
Alzheimer's
disease
(AD),
autism
spectrum
disorder
(ASD),
Rett
syndrome,
attention
deficit
hyperactivity
(ADHD),
non-Alzheimer's
neurodegeneration
dementias,
fronto-temporal
lobe
dementia
(FTLD),
Wilson-Konovalov
(WD),
multisystem
atrophy
(MSA),
Huntington's
chorea
(HC),
Parkinson's
(PD),
multiple
sclerosis
(MS),
amyotrophic
lateral
(ALS),
temporal
epilepsy
(TLE),
depression,
schizophrenia
(SCZ).
Furthermore,
correlation
therapeutics
will
be
discussed.
Conversely,
mood
delivery,
exercise,
psychotropic
agents,
stress,
neurologic
drugs
can
influence
MGBA.
By
understanding
MGBA,
it
may
possible
to
facilitate
into
microbial-based
interventions
therapeutic
strategies
npj Parkinson s Disease,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: Feb. 17, 2024
Abstract
The
brain
renin-angiotensin
system
(RAS)
has
been
related
to
dopaminergic
degeneration,
and
high
expression
of
the
angiotensin
II
(AngII)
type
1
receptor
(AT1)
gene
is
a
marker
most
vulnerable
neurons
in
humans.
However,
it
unknown
whether
AngII/AT1
overactivation
affects
α-synuclein
aggregation
transmission.
In
vitro,
activation
increased
microglial
cells,
which
was
AngII-induced
NADPH-oxidase
intracellular
calcium
raising.
mice,
involved
MPTP-induced
increase
aggregation,
as
they
significantly
decreased
mice
treated
with
AT1
blocker
telmisartan
knockout
mice.
Cell
co-cultures
(transwells)
revealed
strong
transmission
from
astrocytes
microglia.
AngII
induced
higher
uptake
by
cells
an
transfer
among
astroglial
cells.
did
not
release
neurons.
results
further
support
RAS
dysregulation
major
mechanism
for
progression
Parkinson’s
disease,
inhibition
modulation
therapeutic
targets.
Translational Neurodegeneration,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: April 15, 2024
Abstract
The
renin-angiotensin
system
(RAS)
was
classically
considered
a
circulating
hormonal
that
regulates
blood
pressure.
However,
different
tissues
and
organs,
including
the
brain,
have
local
paracrine
RAS.
Mutual
regulation
between
dopaminergic
RAS
has
been
observed
in
several
tissues.
Dysregulation
of
these
interactions
leads
to
renal
cardiovascular
diseases,
as
well
progression
neuron
degeneration
major
brain
center
dopamine/angiotensin
interaction
such
nigrostriatal
system.
A
decrease
function
induces
upregulation
angiotensin
type-1
(AT1)
receptor
activity,
leading
recovery
dopamine
levels.
AT1
overactivity
neurons
microglial
cells
upregulates
cellular
NADPH-oxidase-superoxide
axis
Ca
2+
release,
which
mediate
key
events
oxidative
stress,
neuroinflammation,
α-synuclein
aggregation,
involved
Parkinson's
disease
(PD)
pathogenesis.
An
intraneuronal
antioxidative/anti-inflammatory
counteracts
effects
pro-oxidative
overactivity.
Consistent
with
this,
an
imbalance
activity
towards
pro-oxidative/pro-inflammatory
substantia
nigra
striatum
animal
models
high
vulnerability
degeneration.
Interestingly,
autoantibodies
against
angiotensin-converting
enzyme
2
receptors
are
increased
PD
patients
contribute
blood–brain
barrier
(BBB)
dysregulation
pro-inflammatory
upregulation.
Therapeutic
strategies
addressed
modulation
RAS,
by
blockers
(ARBs)
and/or
activation
antioxidative
(AT2,
Mas
receptors),
may
be
neuroprotective
for
individuals
risk
developing
or
prodromal
stages
reduce
disease.
Alzheimer s & Dementia,
Journal Year:
2024,
Volume and Issue:
20(8), P. 5757 - 5770
Published: June 21, 2024
Abstract
INTRODUCTION
The
recent
introduction
of
seed
amplification
assays
(SAAs)
detecting
misfolded
α‐synuclein,
a
pathology‐specific
marker
for
Lewy
body
disease
(LBD),
has
allowed
the
in
vivo
identification
and
phenotypic
characterization
patients
with
co‐occurring
Alzheimer's
(AD)
LBD
since
early
clinical
or
even
preclinical
stage.
METHODS
We
reviewed
studies
an
biomarker‐based
diagnosis
AD‐LBD
copathology.
RESULTS
Studies
large
cohorts
cognitively
impaired
individuals
have
shown
that
cerebrospinal
fluid
(CSF)
biomarkers
detect
coexistence
AD
LB
pathology
approximately
20%–25%
them,
independently
primary
diagnosis.
Compared
to
those
pure
AD,
showed
worse
global
cognition,
especially
attentive/executive
visuospatial
functions,
motor
functions.
In
unimpaired
individuals,
concurrent
pathologies
predicted
longitudinal
cognitive
progression
faster
worsening
memory,
DISCUSSION
Future
research
aiming
better
precision
medicine
approach
should
develop
SAAs
further
reach
quantitative
evaluation
staging
each
underlying
using
single
biofluid
sample.
Highlights
α‐Synuclein
provide
specific
(LBD).
allow
(AD).
coexist
20‐25%
elderly
∼8%
asymptomatic.
causes
is
associated
attentive/executive,
