Expert Review of Neurotherapeutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 6, 2025
Frontotemporal
dementia
(FTD)
encompasses
a
group
of
heterogeneous
neurodegenerative
disorders.
Aside
from
genetic
cases,
its
diagnosis
is
challenging,
particularly
in
the
early
stages
when
symptoms
are
ambiguous,
and
structural
neuroimaging
does
not
reveal
characteristic
patterns.
The
authors
performed
comprehensive
literature
search
through
MEDLINE,
Scopus,
Web
Science
databases
to
gather
evidence
aid
diagnostic
process
for
suspected
FTD
patients,
phases,
even
sporadic
ranging
established
promising
tools.
Blood-based
biomarkers
might
help
identify
very
neuropathological
guide
further
evaluations.
Subsequently,
neurophysiological
measures
reflecting
functional
changes
cortical
excitatory/inhibitory
circuits,
along
with
assessing
brain
network,
connectivity,
metabolism,
perfusion
alterations,
could
detect
specific
associated
decades
before
symptom
onset.
As
advances,
cognitive-behavioral
profiles
atrophy
patterns
emerge,
distinguishing
subtypes.
Emerging
disease-modifying
therapies
require
patient
enrollment.
Therefore,
paradigm
shift
needed
-
relying
on
typical
cognitive
advanced
cases
widely
applicable
biomarkers,
primarily
fluid
and,
subsequently,
where
appropriate.
Additionally,
exploring
subjective
complaints
behavioral
detected
by
home-based
technologies
be
crucial
diagnosis.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Дек. 16, 2022
Aging
is
a
gradual
and
irreversible
pathophysiological
process.
It
presents
with
declines
in
tissue
cell
functions
significant
increases
the
risks
of
various
aging-related
diseases,
including
neurodegenerative
cardiovascular
metabolic
musculoskeletal
immune
system
diseases.
Although
development
modern
medicine
has
promoted
human
health
greatly
extended
life
expectancy,
aging
society,
variety
chronic
diseases
have
gradually
become
most
important
causes
disability
death
elderly
individuals.
Current
research
on
focuses
elucidating
how
endogenous
exogenous
stresses
(such
as
genomic
instability,
telomere
dysfunction,
epigenetic
alterations,
loss
proteostasis,
compromise
autophagy,
mitochondrial
cellular
senescence,
stem
exhaustion,
altered
intercellular
communication,
deregulated
nutrient
sensing)
participate
regulation
aging.
Furthermore,
thorough
pathogenesis
to
identify
interventions
that
promote
longevity
caloric
restriction,
microbiota
transplantation,
nutritional
intervention)
clinical
treatment
methods
for
(depletion
senescent
cells,
therapy,
antioxidative
anti-inflammatory
treatments,
hormone
replacement
therapy)
could
decrease
incidence
turn
healthy
longevity.
Advanced Drug Delivery Reviews,
Год журнала:
2023,
Номер
197, С. 114822 - 114822
Опубликована: Апрель 21, 2023
Central
nervous
system
(CNS)
disorders
affect
as
many
1.5
billion
people
globally.
The
limited
delivery
of
most
imaging
and
therapeutic
agents
into
the
brain
is
a
major
challenge
for
treatment
CNS
disorders.
With
advent
nanotechnologies,
controlled
drugs
with
nanoparticles
holds
great
promise
in
overcoming
blood-brain
barrier
(BBB)
improving
efficacy.
In
recent
years,
magnetic
iron
oxide
(MIONPs)
have
stood
out
promising
theranostic
nanoplatform
drug
they
possess
unique
physical
properties
biodegradable
characteristics.
this
review,
we
summarize
advances
MIONP-based
platforms
diseases.
We
firstly
introduce
methods
synthesis
surface
functionalization
MIONPs
emphasis
on
inclusion
biocompatible
polymers
that
allow
addition
tailored
physicochemical
properties.
then
discuss
vivo
applications
using
MIONPs.
Finally,
present
perspective
remaining
challenges
possible
future
directions
systems.
Journal of Controlled Release,
Год журнала:
2024,
Номер
367, С. 402 - 424
Опубликована: Фев. 2, 2024
Alzheimer's
disease
(AD),
is
a
neurodegenerative
disorder
that
escalates
with
time,
exerting
significant
impact
on
physical
and
mental
health
leading
to
death.
The
prevalence
of
AD
progressively
rising
along
its
associated
economic
burden
necessitates
effective
therapeutic
approaches
in
the
near
future.
This
review
paper
aims
offer
an
insightful
overview
pathogenesis,
current
FDA-approved
drugs,
drugs
different
clinical
phases.
It
also
explores
innovative
formulations
drug
delivery
strategies,
focusing
nanocarriers
long-acting
medications
(LAMs)
enhance
treatment
efficacy
patient
adherence.
emphasizes
preclinical
evidence
related
their
potential
improve
bioavailability,
pharmacokinetics,
pharmacodynamics
parameters,
while
highlighting
ability
minimize
systemic
side
effects.
By
providing
comprehensive
analysis,
this
furnishes
valuable
insights
into
pathophysiological
mechanisms
for
future
development.
inform
development
strategies
formulation
delivering
existing
molecules
disease,
ultimately
striving
compliance.
Experimental Gerontology,
Год журнала:
2024,
Номер
188, С. 112389 - 112389
Опубликована: Март 8, 2024
Aging-related
diseases
(ARDs)
are
a
major
global
health
concern,
and
the
development
of
effective
therapies
is
urgently
needed.
Kaempferol,
flavonoid
found
in
several
plants,
has
emerged
as
promising
candidate
for
ameliorating
ARDs.
This
comprehensive
review
examines
Kaempferol's
chemical
properties,
safety
profile,
pharmacokinetics,
highlights
its
potential
therapeutic
utility
against
underpinned
by
distinctive
structure,
which
confers
antioxidative
anti-inflammatory
properties.
Kaempferol
counteracts
reactive
oxygen
species
(ROS)
modulates
crucial
cellular
pathways,
thereby
combating
oxidative
stress
inflammation,
hallmarks
low
toxicity
wide
margins,
demonstrated
preclinical
clinical
studies,
further
substantiate
potential.
Compelling
evidence
supports
substantial
addressing
ARDs
through
mechanisms,
notably
anti-inflammatory,
antioxidant,
anti-apoptotic
actions.
exhibits
versatile
neuroprotective
effect
modulating
various
proinflammatory
signaling
including
NF-kB,
p38MAPK,
AKT,
β-catenin
cascade.
Additionally,
it
hinders
formation
aggregation
beta-amyloid
protein
regulates
brain-derived
neurotrophic
factors.
In
terms
anticancer
potential,
kaempferol
acts
diverse
inducing
apoptosis,
arresting
cell
cycle
at
G2/M
phase,
suppressing
epithelial-mesenchymal
transition
(EMT)-related
markers,
affecting
phosphoinositide
3-kinase/protein
kinase
B
pathways.
Subsequent
studies
should
focus
on
refining
dosage
regimens,
exploring
innovative
delivery
systems,
conducting
trials
to
translate
these
findings
into
applications.
Acta Neuropathologica,
Год журнала:
2024,
Номер
147(1)
Опубликована: Фев. 12, 2024
Abstract
Central
nervous
system
(CNS)
accumulation
of
fibrillary
deposits
made
Amyloid
β
(A
),
hyperphosphorylated
Tau
or
α
-synuclein
(
-syn),
present
either
alone
in
the
form
mixed
pathology,
characterizes
most
common
neurodegenerative
diseases
(NDDs)
as
well
aging
brain.
Compelling
evidence
supports
that
acute
neurological
disorders,
such
traumatic
brain
injury
(TBI)
and
stroke,
are
also
accompanied
by
increased
deposition
toxic
A
,
-syn
species.
While
contribution
these
pathological
proteins
to
neurodegeneration
has
been
experimentally
ascertained,
cellular
molecular
mechanisms
driving
-syn-related
damage
remain
be
fully
clarified.
In
last
few
years,
studies
have
shown
may
contribute
inducing
and/or
promoting
blood–brain
barrier
(BBB)
disruption.
These
can
affect
BBB
integrity
directly
affecting
key
components
pericytes
endothelial
cells
(ECs)
indirectly,
macrophages
activation
dysfunction.
Here,
we
summarize
critically
discuss
findings
showing
how
NDDs,
TBI
stroke.
We
highlight
need
for
a
deeper
characterization
role
dysfunction
macrophages,
ECs
improve
diagnosis
treatment
chronic
disorders.
Neuron,
Год журнала:
2024,
Номер
112(18), С. 3106 - 3125.e8
Опубликована: Июль 25, 2024
Microglia
are
crucial
for
maintaining
brain
health
and
neuron
function.
Here,
we
report
that
microglia
establish
connections
with
neurons
using
tunneling
nanotubes
(TNTs)
in
both
physiological
pathological
conditions.
These
TNTs
facilitate
the
rapid
exchange
of
organelles,
vesicles,
proteins.
In
neurodegenerative
diseases
like
Parkinson's
Alzheimer's
disease,
toxic
aggregates
alpha-synuclein
(α-syn)
tau
accumulate
within
neurons.
Our
research
demonstrates
use
to
extract
from
these
aggregates,
restoring
neuronal
health.
Additionally,
share
their
healthy
mitochondria
burdened
neurons,
reducing
oxidative
stress
normalizing
gene
expression.
Disrupting
mitochondrial
function
antimycin
A
before
TNT
formation
eliminates
this
neuroprotection.
Moreover,
co-culturing
promoting
rescues
suppressed
activity
caused
by
α-syn
or
aggregates.
Notably,
TNT-mediated
aggregate
transfer
is
compromised
carrying
Lrrk22(Gly2019Ser)
Trem2(T66M)
(R47H)
mutations,
suggesting
a
role
pathology
variants
diseases.
Acta Neuropathologica,
Год журнала:
2024,
Номер
147(1)
Опубликована: Янв. 10, 2024
Abstract
Alpha-synuclein
(aSyn)
pathology
is
present
in
approximately
50%
of
Alzheimer’s
disease
(AD)
cases
at
autopsy
and
might
impact
the
age-of-onset
progression
AD.
Here,
we
aimed
to
determine
whether
tau
aSyn
profiles
differ
between
AD
with
Lewy
bodies
(AD-LB),
pure
Parkinson’s
dementia
(PDD)
using
epitope-,
post-translational
modification-
(PTM)
isoform-specific
antibody
panels
spanning
from
N-
C-terminus.
We
included
middle
temporal
gyrus
(MTG)
amygdala
(AMY)
clinically
diagnosed
pathologically
confirmed
performed
dot
blotting,
western
blotting
immunohistochemistry
combined
quantitative
morphological
analyses.
All
investigated
phospho-tau
(pTau)
species,
except
pT181,
were
upregulated
AD-LB
compared
PDD
control
cases,
but
no
significant
differences
observed
subjects.
In
addition,
antibodies
targeting
proline-rich
regions
C-terminus
showed
preferential
binding
brain
homogenates.
Antibodies
C-terminal
epitopes
pS129
stronger
cases.
Two
pTau
species
(pS198
pS396)
specifically
detected
soluble
protein
fractions
subjects,
indicative
early
involvement
these
PTMs
multimerization
process
tau.
Other
phospho-variants
for
both
(pT212/S214,
pT231
pS422)
(pS129)
only
insoluble
fraction
AD-LB/AD
AD-LB/PDD
respectively.
load
was
higher
AMY
suggesting
aggravated
under
presence
pathology,
while
similar
Co-localization
could
be
within
astrocytes
MTG.
These
findings
highlight
a
unique
pathological
signature
