MedComm – Biomaterials and Applications,
Год журнала:
2023,
Номер
2(2)
Опубликована: Июнь 1, 2023
Abstract
With
the
aging
of
global
population,
early
diagnosis
and
treatment
neurodegenerative
diseases
such
as
Parkinson's
disease
(PD)
have
attracted
considerable
attention.
Despite
great
advances
achieved
during
past
decades,
PD
second
largest
is
still
incurable.
In
clinical
practice,
patients
are
mainly
treated
by
drugs,
supplemented
with
deep
brain
stimulation
or
nerve
nucleus
destruction.
The
existing
drugs
can
only
relieve
symptoms
motor
disorder,
cannot
stop
progression
PD.
Compared
small
molecular
nanoparticles
exhibit
multiple
functions
in
neuroprotection
neurorepair
due
to
their
tunable
physical
chemical
properties,
easy
modification
functionalization.
Herein,
we
first
briefly
review
characteristics
crossing
blood–brain
barrier,
which
a
primary
challenge
for
Then,
summarize
pathologic
mechanisms
comprehensively
discuss
novel
therapy
based
on
diverse
nanoparticles,
including
alleviating
oxidative
stress,
scavenging
α‐synuclein
aggregates,
chelating
metal
ions,
delivering
neurotrophic
factors
genes,
transplanting
stem
cells.
This
aims
highlight
potential
advanced
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Янв. 1, 2024
Abstract
Combining
existing
drug
therapy
is
essential
in
developing
new
therapeutic
agents
disease
prevention
and
treatment.
In
preclinical
investigations,
combined
effect
of
certain
known
drugs
has
been
well
established
treating
extensive
human
diseases.
Attributed
to
synergistic
effects
by
targeting
various
pathways
advantages,
such
as
reduced
administration
dose,
decreased
toxicity,
alleviated
resistance,
combinatorial
treatment
now
being
pursued
delivering
combat
major
clinical
illnesses,
cancer,
atherosclerosis,
pulmonary
hypertension,
myocarditis,
rheumatoid
arthritis,
inflammatory
bowel
disease,
metabolic
disorders
neurodegenerative
Combinatorial
involves
combining
or
co-delivering
two
more
for
a
specific
disease.
Nanoparticle
(NP)-mediated
delivery
systems,
i.e.,
liposomal
NPs,
polymeric
NPs
nanocrystals,
are
great
interest
wide
range
due
targeted
delivery,
extended
release,
higher
stability
avoid
rapid
clearance
at
infected
areas.
This
review
summarizes
targets
diseases,
clinically
approved
combinations
the
development
multifunctional
emphasizes
strategies
based
on
severe
Ultimately,
we
discuss
challenging
NP-codelivery
translation
provide
potential
approaches
address
limitations.
offers
comprehensive
overview
recent
cutting-edge
NP-mediated
combination
Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Ноя. 11, 2023
Abstract
Mitochondrial
dysfunction
is
strongly
implicated
in
the
etiology
of
idiopathic
and
genetic
Parkinson’s
disease
(PD).
However,
strategies
aimed
at
ameliorating
mitochondrial
dysfunction,
including
antioxidants,
antidiabetic
drugs,
iron
chelators,
have
failed
disease-modification
clinical
trials.
In
this
review,
we
summarize
cellular
determinants
impairment
electron
transport
chain
complex
1,
increased
oxidative
stress,
disturbed
quality
control
mechanisms,
bioenergetic
deficiency.
addition,
outline
pathways
to
neurodegeneration
current
context
PD
pathogenesis,
review
past
treatment
an
attempt
better
understand
why
translational
efforts
thus
far
been
unsuccessful.
Inflammopharmacology,
Год журнала:
2022,
Номер
31(1), С. 37 - 56
Опубликована: Дек. 29, 2022
Abstract
Silent
information
regulator
(SIRT)
has
distinctive
enzymatic
activities
and
physiological
functions
to
control
cell-cycle
progression,
gene
expression,
DNA
stability
by
targeting
histone
non-histone
proteins.
SIRT1
enhances
synaptic
formation
activity,
therefore,
can
reduce
the
progression
of
various
degenerative
brain
diseases
including
Parkinson’s
disease
(PD).
activity
is
decreased
aging
with
a
subsequent
increased
risk
for
development
diseases.
Inhibition
promotes
inflammatory
reactions
since
inhibits
transcription
nuclear
factor
kappa
B
(NF-κB)
which
also
activation
via
microRNA
miR-34a
NAD
synthesis.
highly
expressed
in
microglia
as
well
neurons,
antioxidant
anti-inflammatory
effects.
Therefore,
this
review
aimed
find
possible
role
PD
neuropathology.
neuroprotective
effects;
downregulation
during
p53
expression
may
increase
vulnerability
neuronal
cell
deaths.
neuropathology
linked
sequence
changes
release
pro-inflammatory
cytokines
due
signaling
pathways.
In
addition,
oxidative
stress,
disorders,
mitochondrial
dysfunction,
apoptosis
contribute
mutually
Thus,
activators
play
crucial
mitigation
through
amelioration
apoptosis,
Acta Neuropathologica Communications,
Год журнала:
2024,
Номер
12(1)
Опубликована: Июль 2, 2024
Abstract
The
genetic
architecture
of
Parkinson’s
disease
(PD)
is
complex
and
multiple
brain
cell
subtypes
are
involved
in
the
neuropathological
progression
disease.
Here
we
aimed
to
advance
our
understanding
PD
complexity
at
a
subtype
precision
level.
Using
parallel
single-nucleus
(sn)RNA-seq
snATAC-seq
analyses
simultaneously
profiled
transcriptomic
chromatin
accessibility
landscapes
temporal
cortex
tissues
from
12
compared
control
subjects
granular
single
resolution.
An
integrative
bioinformatic
pipeline
was
developed
applied
for
these
snMulti-omics
datasets.
results
identified
subpopulation
cortical
glutamatergic
excitatory
neurons
with
remarkably
altered
gene
expression
PD,
including
differentially-expressed
genes
within
risk
loci
genome-wide
association
studies
(GWAS).
This
only
neuronal
showing
significant
robust
overexpression
SNCA
.
Further
characterization
this
neuronal-subpopulation
showed
upregulation
specific
pathways
related
axon
guidance,
neurite
outgrowth
post-synaptic
structure,
downregulated
presynaptic
organization
calcium
response.
Additionally,
characterized
roles
three
molecular
mechanisms
governing
PD-associated
subtype-specific
dysregulation
expression:
(1)
changes
cis-regulatory
element
transcriptional
machinery;
(2)
abundance
master
regulators,
YY1,
SP3,
KLF16;
(3)
candidate
regulatory
variants
high
linkage
disequilibrium
PD-GWAS
genomic
impacting
transcription
factor
binding
affinities.
To
knowledge,
study
first
most
comprehensive
interrogation
multi-omics
landscape
cell-subtype
Our
findings
provide
new
insights
into
precise
subtype,
causal
genes,
non-coding
underlying
paving
way
development
cell-
gene-targeted
therapeutics
halt
as
well
biomarkers
early
preclinical
diagnosis.
Biology,
Год журнала:
2024,
Номер
13(9), С. 719 - 719
Опубликована: Сен. 12, 2024
Neurodegenerative
diseases
(NDs),
like
amyotrophic
lateral
sclerosis
(ALS),
Alzheimer's
disease
(AD),
and
Parkinson's
(PD),
primarily
affect
the
central
nervous
system,
leading
to
progressive
neuronal
loss
motor
cognitive
dysfunction.
However,
recent
studies
have
revealed
that
muscle
tissue
also
plays
a
significant
role
in
these
diseases.
ALS
is
characterized
by
severe
wasting
as
result
of
neuron
degeneration,
well
alterations
gene
expression,
protein
aggregation,
oxidative
stress.
Muscle
atrophy
mitochondrial
dysfunction
are
observed
AD,
which
may
exacerbate
decline
due
systemic
metabolic
dysregulation.
PD
patients
exhibit
fiber
atrophy,
altered
composition,
α-synuclein
aggregation
within
cells,
contributing
symptoms
progression.
Systemic
inflammation
impaired
degradation
pathways
common
among
disorders,
highlighting
key
player
Understanding
muscle-related
changes
offers
potential
therapeutic
avenues,
such
targeting
function,
reducing
inflammation,
promoting
regeneration
with
exercise
pharmacological
interventions.
This
review
emphasizes
importance
considering
an
integrative
approach
neurodegenerative
research,
both
peripheral
pathological
mechanisms,
order
develop
more
effective
treatments
improve
patient
outcomes.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 19, 2023
Abstract
NEMO
is
a
ubiquitin-binding
protein
which
regulates
canonical
NF-κB
pathway
activation
in
innate
immune
signaling,
cell
death
regulation
and
host-pathogen
interactions.
Here
we
identify
an
NF-κB-independent
function
of
proteostasis
by
promoting
autophagosomal
clearance
aggregates.
NEMO-deficient
cells
accumulate
misfolded
proteins
upon
proteotoxic
stress
are
vulnerable
to
challenges.
Moreover,
patient
with
mutation
the
NEMO-encoding
IKBKG
gene
resulting
defective
binding
linear
ubiquitin
chains,
developed
widespread
mixed
brain
proteinopathy,
including
α-synuclein,
tau
TDP-43
pathology.
amplifies
ubiquitylation
at
α-synuclein
aggregates
promotes
local
concentration
p62
into
foci.
In
vitro,
lowers
threshold
concentrations
required
for
ubiquitin-dependent
phase
transition
p62.
summary,
reshapes
aggregate
surface
efficient
providing
mobile
interphase
favoring
co-condensation
Journal of Molecular Biology,
Год журнала:
2022,
Номер
435(12), С. 167930 - 167930
Опубликована: Дек. 22, 2022
The
progressive
accumulation
of
insoluble
aggregates
the
presynaptic
protein
alpha-synuclein
(α-Syn)
is
a
hallmark
neurodegenerative
disorders
including
Parkinson's
disease
(PD),
Multiple
System
Atrophy,
and
Dementia
with
Lewy
Bodies,
commonly
referred
to
as
synucleinopathies.
Despite
considerable
progress
on
structural
biology
these
aggregates,
molecular
mechanisms
mediating
their
cell-to-cell
transmission,
propagation,
neurotoxicity
remain
only
partially
understood.
Numerous
studies
have
highlighted
stereotypical
spatiotemporal
spreading
pathological
α-Syn
across
different
tissues
anatomically
connected
brain
regions
over
time.
Experimental
evidence
from
various
cellular
animal
models
indicate
that
transfer
occurs
in
two
defined
steps:
release
pathogenic
species
infected
cells,
uptake
via
passive
or
active
endocytic
pathways.
Once
been
internalized,
little
known
about
what
drives
toxicity
how
they
interact
endogenous
promote
its
misfolding
subsequent
aggregation.
Similarly,
unknown
genetic
factors
modulate
responses
aggregation
species.
Here
we
discuss
current
understanding
phenomena
associated
intercellular
seeds
summarize
supporting
transmission
hypothesis.
Understanding
involved
essential
develop
novel
targeted
therapeutics
against
PD
related
