Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 13, 2025
Abstract
Organelles
are
specialized
subunits
within
cells
which
carry
out
vital
functions
crucial
to
cellular
survival
and
form
a
tightly
regulated
network.
Dysfunctions
in
any
of
these
organelles
linked
numerous
diseases
impacting
virtually
every
organ
system
the
human
body.
Targeted
delivery
therapeutics
specific
cell
holds
great
promise
for
overcoming
challenging
improving
treatment
outcomes
through
minimization
therapeutic
dosage
off‐target
effects.
Nanoparticles
versatile
effective
tools
organelles.
offer
several
advantageous
characteristics,
including
high
surface
area‐to‐volume
ratio
efficient
loading
ability
attach
targeting
moieties
(tethers)
that
enhance
delivery.
The
choice
nanoparticle
shape,
size,
composition,
properties,
ligands
depends
on
desired
target
organelle
effect.
Various
platforms
have
been
explored
targeting,
such
as
liposomes,
polymeric
nanoparticles,
dendrimers,
inorganic
nanoparticles.
In
this
review,
current
emerging
approaches
design
examined
context
various
dysfunction.
Specifically,
advances
therapies
nucleus,
mitochondria,
lysosomes/endosomes,
Golgi
apparatus,
endoplasmic
reticulum
comprehensively
critically
discussed.
The Science of The Total Environment,
Journal Year:
2025,
Volume and Issue:
969, P. 178972 - 178972
Published: Feb. 28, 2025
While
emerging
evidence
links
per-
and
polyfluoroalkyl
substances
(PFAS)
to
neurotoxicity,
their
potential
role
in
neurodegeneration
remains
poorly
understood.
Moreover,
existing
neurodegeneration-related
adverse
outcome
pathways
(AOPs)
available
on
AOP-Wiki
have
not
yet
been
integrated
into
a
unified
network.
To
address
these
gaps,
this
study
aims
develop
the
first
AOP
network
utilize
it
explore
possible
contributions
of
long-chain
legacy
PFAS
neurodegeneration,
specifically
concerning
Alzheimer's
Parkinson's
diseases.
A
total
74
AOPs
were
screened
from
AOP-Wiki,
which
13
met
eligibility
criteria
incorporated
We
analyzed
resulting
using
topological
parameters
such
as
in-degree,
out-degree,
eccentricity,
betweenness
centrality.
elucidate
mechanistic
exposure
neurodegenerative
pathways,
we
linking
key
events
(KEs)
within
The
results
highlighted
increased
intracellular
calcium
hub
with
highest
connectivity
followed
by
critical
KEs
neuronal
apoptosis,
oxidative
stress,
N-methyl-d-aspartate
receptor
(NMDA-R)
overactivation,
mitochondrial
dysfunction.
Consistent
toxicological
evidence,
indicate
that
may
adversely
affect
neurotransmitter
systems,
particularly
through
NMDA-R
leading
excitotoxicity.
This
result
dyshomeostasis,
dysfunction,
inflammatory-oxidative
cascades,
neuroinflammation,
cell
death.
By
providing
basis
for
understanding
PFAS,
offers
crucial
framework
assessing
risks
associated
chemicals
inform
future
regulatory
measures
public
health
strategies.
Further
experimental
validation
is
needed
confirm
animal
models
or
human
populations.
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(6), P. 2108 - 2108
Published: March 19, 2020
Higher
prevalence
of
neurodegenerative
diseases
is
strictly
connected
with
progressive
aging
the
world
population.
Interestingly,
a
broad
range
age-related,
characterized
by
common
pathological
mechanism—accumulation
misfolded
and
unfolded
proteins
within
cells.
Under
certain
circumstances,
such
protein
aggregates
may
evoke
endoplasmic
reticulum
(ER)
stress
conditions
subsequent
activation
response
(UPR)
signaling
pathways
via
kinase
RNA-like
(PERK)-dependent
manner.
mild
to
moderate
ER
stress,
UPR
has
pro-adaptive
role.
However,
severe
or
long-termed
directly
shift
toward
its
pro-apoptotic
branch,
which
considered
be
possible
cause
neurodegeneration.
To
this
day,
there
no
effective
cure
for
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
Huntington’s
(HD),
prion
disease.
Currently
available
treatment
approaches
these
are
only
symptomatic
cannot
affect
progression.
Treatment
strategies,
currently
under
detailed
research,
include
inhibition
PERK-dependent
branches.
The
newest
data
have
reported
that
use
small-molecule
inhibitors
PERK-mediated
branches
contribute
development
novel,
ground-breaking
therapeutic
approach
In
review,
we
critically
describe
all
aspects
associated
targeted
therapy
against
proteopathies.
Acta Neuropathologica Communications,
Journal Year:
2020,
Volume and Issue:
8(1)
Published: April 21, 2020
Abstract
The
etiology
of
Parkinson’s
disease
is
largely
unknown.
Genome-wide
transcriptomic
studies
in
bulk
brain
tissue
have
identified
several
molecular
signatures
associated
with
the
disease.
While
these
potential
to
shed
light
into
pathogenesis
disease,
they
are
also
limited
by
two
major
confounders:
RNA
post-mortem
degradation
and
heterogeneous
cell
type
composition
samples.
We
performed
sequencing
following
ribosomal
depletion
prefrontal
cortex
49
individuals
from
independent
case-control
cohorts.
Using
specific
markers,
we
estimated
for
each
sample
included
this
our
analysis
models
compensate
variation
proportions.
Ribosomal
followed
capture
random
primers
resulted
substantially
more
even
transcript
coverage,
compared
poly(A)
capture,
tissue.
Moreover,
show
that
a
confounder
differential
gene
expression
brain.
Accounting
proportions
attenuated
numerous
been
previously
including
vesicle
trafficking,
synaptic
transmission,
immune
mitochondrial
function.
Conversely,
pathways
related
endoplasmic
reticulum,
lipid
oxidation
unfolded
protein
response
were
strengthened
surface
as
top
cortex.
Our
results
indicate
significantly
confounded
underlying
differences
composition.
Modeling
heterogeneity
crucial
order
unveil
represent
regulatory
changes
are,
therefore,
likely
be
mechanisms.
