Molecular Neurodegeneration,
Год журнала:
2019,
Номер
14(1)
Опубликована: Авг. 16, 2019
Cell-to-cell
propagation
of
α-synuclein
(α-syn)
aggregates
is
thought
to
contribute
the
pathogenesis
Parkinson's
disease
(PD)
and
underlie
spread
α-syn
neuropathology.
Increased
pro-inflammatory
cytokine
levels
activated
microglia
are
present
in
PD
can
promote
aggregation.
However,
it
unclear
how
influence
cell-to-cell
transfer.
We
developed
a
clinically
relevant
mouse
model
monitor
prion-like
between
cells;
we
transplanted
wild-type
embryonic
midbrain
neurons
into
striatum
overexpressing
human
(huα-syn)
following
adeno-associated
viral
injection
substantia
nigra.
In
this
system,
depleted
or
microglial
cells
determined
effects
on
transfer
huα-syn
from
host
nigrostriatal
implanted
dopaminergic
neurons,
using
presence
within
grafted
as
readout.
First,
compared
mice
with
normal
number
which
had
pharmacologically
ablated
80%
striatum.
With
fewer
microglia,
observed
increased
accumulation
neurons.
Second,
assessed
context
by
one
two
stimuli,
lipopolysaccharide
(LPS)
interleukin-4
(IL-4).
LPS
exposure
led
strong
activation
(as
morphology,
production
an
upregulation
genes
involved
inflammatory
response
LPS-injected
RNA
sequencing
analysis).
significantly
higher
amounts
contrast,
IL-4
did
not
change
proportion
dopamine
that
contained
relative
controls.
As
expected,
analysis
striatal
tissue
revealed
differential
gene
expression
IL-4-injected
mice;
upregulated
injected
including
several
those
response.
The
absence
hyperstimulation
affected
brain.
Our
results
suggest
under
resting,
non-inflammatory
conditions,
modulate
α-syn.
Pharmacological
regulation
neuroinflammation
could
represent
future
avenue
for
limiting
Theranostics,
Год журнала:
2022,
Номер
12(9), С. 4310 - 4329
Опубликована: Янв. 1, 2022
Pyroptosis
is
a
lytic
and
inflammatory
type
of
programmed
cell
death
that
usually
triggered
by
inflammasomes
executed
gasdermin
proteins.
The
main
characteristics
pyroptosis
are
swelling,
membrane
perforation,
the
release
contents.
In
normal
physiology,
plays
critical
role
in
host
defense
against
pathogen
infection.
However,
excessive
may
cause
immoderate
continuous
responses
involves
occurrence
diseases.
Attractively,
as
immunogenic
death,
can
serve
new
strategy
for
cancer
elimination
inducing
pyroptotic
activating
intensely
antitumor
immunity.
To
make
good
use
this
double-edged
sword,
molecular
mechanisms,
therapeutic
implications
related
diseases
need
to
be
fully
elucidated.
review,
we
first
systematically
summarize
signaling
pathways
then
present
available
evidences
indicating
cancer.
Based
on
this,
focus
recent
progress
strategies
inhibit
treatment
diseases,
those
induce
therapy.
Overall,
should
shed
light
future
directions
provide
novel
ideas
using
powerful
tool
fight
Cell Death and Differentiation,
Год журнала:
2021,
Номер
28(2), С. 570 - 590
Опубликована: Янв. 7, 2021
Abstract
Neurodegenerative
diseases
are
characterised
by
progressive
damage
to
the
nervous
system
including
selective
loss
of
vulnerable
populations
neurons
leading
motor
symptoms
and
cognitive
decline.
Despite
millions
people
being
affected
worldwide,
there
still
no
drugs
that
block
neurodegenerative
process
stop
or
slow
disease
progression.
Neuronal
death
in
these
is
often
linked
misfolded
proteins
aggregate
within
brain
(proteinopathies)
as
a
result
disease-related
gene
mutations
abnormal
protein
homoeostasis.
There
two
major
degradation
pathways
rid
cell
unwanted
prevent
their
accumulation
maintain
health
cell:
ubiquitin–proteasome
autophagy–lysosomal
pathway.
Both
degradative
depend
on
modification
targets
with
ubiquitin.
Aging
primary
risk
factor
most
Alzheimer’s
disease,
Parkinson’s
amyotrophic
lateral
sclerosis.
With
aging
general
reduction
proteasomal
autophagy,
consequent
increase
potentially
neurotoxic
aggregates
β-amyloid,
tau,
α-synuclein,
SOD1
TDP-43.
An
over-looked
yet
component
ubiquitin,
implicating
either
an
adaptive
response
toxic
evidence
dysregulated
ubiquitin-mediated
driving
aggregation.
In
addition,
non-degradative
ubiquitin
signalling
critical
for
homoeostatic
mechanisms
fundamental
neuronal
function
survival,
mitochondrial
homoeostasis,
receptor
trafficking
DNA
responses,
whilst
also
playing
role
inflammatory
processes.
This
review
will
discuss
current
understanding
ubiquitin-dependent
processes
emergence
target
development
much
needed
new
treat
disease.
Neurobiology of Disease,
Год журнала:
2020,
Номер
144, С. 105028 - 105028
Опубликована: Июль 28, 2020
While
glia
are
essential
for
regulating
the
homeostasis
in
normal
brain,
their
dysfunction
contributes
to
neurodegeneration
many
brain
diseases,
including
Parkinson's
disease
(PD).
Recent
studies
have
identified
that
PD-associated
genes
expressed
glial
cells
as
well
neurons
and
crucial
roles
microglia
astrocytes.
Here,
we
discuss
role
of
astrocytes
relation
PD-linked
mutations
implications
PD
pathogenesis.
A
better
understanding
astrocyte
functions
may
provide
insights
into
novel
therapeutic
approaches
PD.
Antioxidants,
Год журнала:
2020,
Номер
9(8), С. 647 - 647
Опубликована: Июль 22, 2020
Oxidative
stress
develops
as
a
response
to
injury
and
reflects
breach
in
the
cell’s
antioxidant
capacity.
Therefore,
fine-tuning
of
reactive
oxygen
species
(ROS)
generation
is
crucial
for
preserving
homeostasis.
Mitochondria
are
major
source
an
immediate
target
ROS.
Under
different
stimuli,
including
oxidative
impaired
quality
control,
mitochondrial
constituents
(e.g.,
DNA,
mtDNA)
displaced
toward
intra-
or
extracellular
compartments.
However,
mechanisms
responsible
mtDNA
unloading
remain
largely
unclear.
While
shuttling
freely
within
cell,
can
be
delivered
into
compartment
via
either
extrusion
entire
nucleoids
release
vesicles.
Once
discarded,
may
act
damage-associated
molecular
pattern
(DAMP)
trigger
innate
immune
inflammatory
by
binding
danger-signal
receptors.
Neuroinflammation
associated
with
large
array
neurological
disorders
which
DAMPs
could
represent
common
thread
supporting
disease
progression.
The
exploration
non-canonical
pathways
involved
control
neurodegeneration
unveil
novel
targets
development
therapeutic
agents.
Here,
we
discuss
these
processes
setting
two
neurodegenerative
diseases
(Alzheimer’s
Parkinson’s
disease)
Down
syndrome,
most
frequent
progeroid
syndrome.
Frontiers in Aging Neuroscience,
Год журнала:
2022,
Номер
14
Опубликована: Июнь 10, 2022
The
NLRP3
inflammasome
is
a
multiprotein
complex
that
plays
pivotal
role
in
regulating
the
innate
immune
system
and
inflammatory
signaling.
Upon
activation
by
PAMPs
DAMPs,
oligomerizes
activates
caspase-1
which
initiates
processing
release
of
pro-inflammatory
cytokines
IL-1β
IL-18.
most
extensively
studied
to
date
due
its
array
activators
aberrant
several
diseases.
Studies
using
small
molecules
biologics
targeting
pathway
have
shown
positive
outcomes
treating
various
disease
pathologies
blocking
chronic
inflammation.
In
this
review,
we
discuss
recent
advances
understanding
mechanism,
pathology,
provide
broad
review
therapeutics
discovered
target
their
challenges.
