Molecular Neurodegeneration,
Journal Year:
2019,
Volume and Issue:
14(1)
Published: Aug. 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
Current Nutrition Reports,
Journal Year:
2019,
Volume and Issue:
8(2), P. 53 - 65
Published: April 4, 2019
Nutrition
is
known
to
modulate
the
immune
system
and
may
alter
neuroinflammatory
processes
implicated
in
pathogenesis
of
Alzheimer's
disease
(AD)
progression
neurodegeneration.
Here,
we
review
evidence
for
healthy
dietary
patterns
age-related
cognition
discuss
potential
actions
diet
on
cognitive
function.
Anti-inflammatory
such
as
Mediterranean
(MD)
approaches
stop
hypertension
(DASH)
be
neuroprotective.
Several
components
consumed
MD
DASH
(omega-3
fatty
acids,
antioxidants
polyphenols)
can
inhibit
neuroinflammation
associated
with
AD.
diets
also
attenuate
via
indirect
pathways
from
gut
microbiome
systemic
circulation.
Diet
influence
ageing
several
inflammatory
pathways.
However,
data
human
studies
are
lacking
exact
mechanisms
linking
function
remain
elusive.
Further
intervention
required
investigate
diet-associated
neurological
change
earliest
through
latest
stages
decline.
Furthermore,
incorporation
neuroimaging
measures
would
advance
current
understanding
mechanistic
effects
modification
brain.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Aug. 21, 2020
Abstract
We
describe
a
human
single-nuclei
transcriptomic
atlas
for
the
substantia
nigra
(SN),
generated
by
sequencing
approximately
17,000
nuclei
from
matched
cortical
and
SN
samples.
show
that
common
genetic
risk
Parkinson’s
disease
(PD)
is
associated
with
dopaminergic
neuron
(DaN)-specific
gene
expression,
including
mitochondrial
functioning,
protein
folding
ubiquitination
pathways.
identify
distinct
cell
type
association
between
PD
oligodendrocyte-specific
expression.
Unlike
Alzheimer’s
(AD),
we
find
no
microglia
or
astrocytes,
suggesting
neuroinflammation
plays
less
causal
role
in
than
AD.
Beyond
PD,
associations
DaNs
GABAergic
expression
multiple
neuropsychiatric
disorders.
Conditional
analysis
reveals
disorders
associate
sets
of
neuron-specific
genes
but
converge
onto
shared
loci
within
oligodendrocytes
oligodendrocyte
precursors.
This
guides
our
aetiological
understanding
associating
profiles
specific
risk.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Feb. 16, 2024
Abstract
The
human
gastrointestinal
tract
is
populated
with
a
diverse
microbial
community.
vast
genetic
and
metabolic
potential
of
the
gut
microbiome
underpins
its
ubiquity
in
nearly
every
aspect
biology,
including
health
maintenance,
development,
aging,
disease.
advent
new
sequencing
technologies
culture-independent
methods
has
allowed
researchers
to
move
beyond
correlative
studies
toward
mechanistic
explorations
shed
light
on
microbiome–host
interactions.
Evidence
unveiled
bidirectional
communication
between
central
nervous
system,
referred
as
“microbiota–gut–brain
axis”.
microbiota–gut–brain
axis
represents
an
important
regulator
glial
functions,
making
it
actionable
target
ameliorate
development
progression
neurodegenerative
diseases.
In
this
review,
we
discuss
mechanisms
As
provides
essential
cues
microglia,
astrocytes,
oligodendrocytes,
examine
communications
microbiota
these
cells
during
healthy
states
Subsequently,
diseases
using
metabolite-centric
approach,
while
also
examining
role
microbiota-related
neurotransmitters
hormones.
Next,
targeting
intestinal
barrier,
blood–brain
meninges,
peripheral
immune
system
counteract
dysfunction
neurodegeneration.
Finally,
conclude
by
assessing
pre-clinical
clinical
evidence
probiotics,
prebiotics,
fecal
transplantation
A
thorough
comprehension
will
foster
effective
therapeutic
interventions
for
management
Antioxidants,
Journal Year:
2020,
Volume and Issue:
9(7), P. 597 - 597
Published: July 8, 2020
Parkinson's
disease
(PD)
is
caused
by
progressive
neurodegeneration
of
dopaminergic
(DAergic)
neurons
with
abnormal
accumulation
α-synuclein
in
substantia
nigra
(SN).
Studies
have
suggested
the
potential
involvement
dopamine,
iron,
calcium,
mitochondria
and
neuroinflammation
contributing
to
overwhelmed
oxidative
stress
PD.
Function
studies
on
PD-causative
mutations
SNCA,
PRKN,
PINK1,
DJ-1,
LRRK2,
FBXO7
ATP13A2
further
indicate
role
pathogenesis
Therefore,
it
reasonable
that
molecules
involved
stress,
such
as
coenzyme
Q10,
uric
acid,
8-hydroxy-2'-deoxyguanosin,
homocysteine,
retinoic
acid/carotenes,
vitamin
E,
glutathione
peroxidase,
superoxide
dismutase,
xanthine
oxidase
products
lipid
peroxidation,
could
be
candidate
biomarkers
for
Applications
antioxidants
modulate
a
strategy
treating
Although
number
antioxidants,
creatine,
pioglitazone,
melatonin
desferrioxamine,
been
tested
clinical
trials,
none
them
demonstrated
conclusive
evidence
ameliorate
PD
patients.
Difficulties
may
long-standing
progression
neurodegeneration,
lack
premotor
stage
inadequate
drug
delivery
across
blood-brain
barrier.
Solutions
these
challenges
will
warranted
future
novel
antioxidative
treatment
