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
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(7), P. 2431 - 2431
Published: March 31, 2020
Alzheimer’s
disease
(AD)
and
Parkinson’s
(PD)
are
the
most
common
neurodegenerative
diseases
(NDs),
presenting
a
broad
range
of
symptoms
from
motor
dysfunctions
to
psychobehavioral
manifestations.
A
clinical
course
is
proteinopathy-induced
neural
dysfunction
leading
anatomically
corresponding
neuropathies.
However,
current
diagnostic
criteria
based
on
pathology
symptomatology
little
value
for
sake
prevention
drug
development.
Overviewing
pathomechanism
NDs,
this
review
incorporates
systematic
reviews
inflammatory
cytokines
tryptophan
metabolites
kynurenines
(KYNs)
human
samples,
present
an
inferential
method
explore
potential
links
behind
NDs.
The
results
revealed
increases
pro-inflammatory
neurotoxic
KYNs
in
anti-inflammatory
AD,
PD,
Huntington’s
(HD),
Creutzfeldt–Jakob
disease,
immunodeficiency
virus
(HIV)-associated
neurocognitive
disorders,
decreases
neuromodulatory
HD.
reinforced
strong
link
between
inflammation
KYNs,
confirmed
activation
adaptive
immune
response,
suggested
possible
role
decrease
all
which
may
contribute
development
chronic
low
grade
inflammation.
Commonalities
multifactorial
NDs
were
discussed
limit
criteria,
need
preclinical
biomarkers,
approach
search
initiation
factors
Journal of Neurochemistry,
Journal Year:
2019,
Volume and Issue:
151(6), P. 676 - 688
Published: Sept. 3, 2019
The
single
largest
risk
factor
for
etiology
of
neurodegenerative
diseases
like
Alzheimer's
disease
is
increased
age.
Therefore,
understanding
the
changes
that
occur
as
a
result
aging
central
to
any
possible
prevention
or
cure
such
conditions.
Microglia,
resident
brain
glial
population
most
associated
with
both
protection
neurons
in
health
and
their
destruction
disease,
could
be
significant
player
age
related
changes.
Microglia
can
adopt
an
aberrant
phenotype
sometimes
referred
either
dystrophic
senescent.
While
aged
microglia
have
been
frequently
identified
there
no
conclusive
evidence
proves
causal
role.
This
has
hampered
by
lack
models
microglia.
We
recently
generated
model
senescent
based
on
observation
all
show
iron
overload.
Iron-overloading
cultured
causes
them
take
cause
neurodegeneration
similar
those
observed
patients.
review
considers
how
this
used
determine
role
diseases.
Physiological Reviews,
Journal Year:
2021,
Volume and Issue:
101(3), P. 1047 - 1081
Published: Jan. 21, 2021
The
history
of
Alzheimer's
disease
(AD)
started
in
1907,
but
we
needed
to
wait
until
the
end
century
identify
components
pathological
hallmarks
and
genetic
subtypes
formulate
first
pathogenic
hypothesis.
Thanks
biomarkers
new
technologies,
concept
AD
then
rapidly
changed
from
a
static
view
an
amnestic
dementia
presenium
biological
entity
that
could
be
clinically
manifested
as
normal
cognition
or
different
types.
What
is
clearly
emerging
studies
heterogeneous
each
aspect,
such
amyloid
composition,
tau
distribution,
relation
between
tau,
clinical
symptoms,
background,
thus
it
probably
impossible
explain
with
single
process.
scientific
approach
suffers
chronological
mismatches
clinical,
pathological,
technological
data,
causing
difficulty
conceiving
diagnostic
gold
standards
creating
models
for
drug
discovery
screening.
A
recent
mathematical
computer-based
offers
opportunity
study
real
life
provide
point
final
missing
pieces
puzzle.
Journal of Neuroinflammation,
Journal Year:
2021,
Volume and Issue:
18(1)
Published: Sept. 16, 2021
Microglial-mediated
neuroinflammation
plays
an
important
role
in
vascular
dementia,
and
modulating
has
emerged
as
a
promising
treatment
target.
Nicotinamide
adenine
dinucleotide
(NAD
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
