Journal of Neural Transmission,
Journal Year:
2022,
Volume and Issue:
129(10), P. 1257 - 1270
Published: July 19, 2022
Abstract
Neuromelanin
is
a
black-brownish
pigment,
present
in
so-called
neuromelanin
granules
(NMGs)
the
cell
bodies
of
dopaminergic
neurons
substantia
nigra
(SN)
pars
compacta
.
These
are
lost
neurodegenerative
diseases,
such
as
Parkinson’s
disease
and
dementia
with
Lewy
bodies.
Although
it
known
that
lipids,
proteins,
environmental
toxins
accumulate
NMGs,
function
NMGs
has
not
yet
been
finally
clarified
well
their
origin
synthesis
neuromelanin.
We,
therefore,
isolated
surrounding
SN
tissue
from
control
patients
by
laser
microdissection
analyzed
proteomic
profile
tandem
mass
spectrometry.
With
our
improved
workflow,
we
were
able
to
(1)
strengthen
regularly
reported
link
between
lysosomes,
(2)
detect
tyrosine
hydroxylase
be
highly
abundant
which
may
related
(3)
indicate
undescribed
stress
(SGs)
NMGs.
Based
on
findings,
cautiously
hypothesize,
SGs
or
form
close
proximity
them,
potentially
due
oxidative
caused
neuromelanin-bound
metals.
The
core
pathological
event
in
Parkinson’s
disease
(PD)
is
the
specific
dying
of
dopamine
(DA)
neurons
substantia
nigra
pars
compacta
(SNc).
Why
SNc
DA
are
especially
vulnerable
and
why
idiopathic
PD
has
only
been
found
humans
still
puzzling.
two
main
underlying
factors
neuron
vulnerability
appear
related
to
high
production,
namely
(i)
toxic
effects
cytoplasmic
metabolism
(ii)
continuous
cytosolic
Ca2+
oscillations
absence
Ca2+-buffer
protein
calbindin.
Both
cause
oxidative
stress
by
producing
highly
reactive
quinones
increasing
intra-mitochondrial
concentrations,
respectively.
High
expression
human
cell
bodies
suggested
abundant
presence
DA-derived
pigment
neuromelanin,
which
not
such
abundance
other
species
associated
with
toxicity
at
higher
levels.
created
their
production
system,
despite
that
SN
does
use
unusually
amounts
energy,
explains
sensitive
various
genetic
environmental
create
mitochondrial
damage
thereby
promote
PD.
Aging
increases
multiple
risk
for
PD,
and,
a
large
extent,
accelerated
aging.
To
prevent
neurodegeneration,
possible
approaches
discussed
here
(1)
reducing
accumulation,
(2)
blocking
oscillations,
(3)
providing
bioenergetic
support.
Molecular Neurobiology,
Journal Year:
2024,
Volume and Issue:
61(8), P. 5481 - 5493
Published: Jan. 10, 2024
The
gut-brain
axis
plays
an
important
role
in
Parkinson's
disease
(PD)
by
acting
as
a
route
for
vagal
propagation
of
aggregated
α-synuclein
the
gut-first
endophenotype
and
mediator
gastrointestinal
dyshomeostasis
via
nigro-vagal
pathway
brain-first
disease.
One
mechanism
which
may
promote
PD
is
regulating
redox
homeostasis
overwhelming
evidence
suggests
that
oxidative
stress
key
etiopathogenesis
progression
tract
maintains
organism
critical
barrier
to
environmental
microbiological
electrophilic
challenges.
present
aim
was
utilize
bilateral
intrastriatal
6-hydroxydopamine
(6-OHDA)
model
study
effects
isolated
central
pathology
on
tract.
Three-month-old
male
Wistar
rats
were
either
not
treated
(intact
controls;
CTR)
or
bilaterally
intrastriatally
with
vehicle
(CIS)
6-OHDA
(6-OHDA).
Motor
deficits
assessed
rotarod
performance
test,
duodenum,
ileum,
colon
dissected
biochemical
analyses
12
weeks
after
treatment.
Lipid
peroxidation,
total
antioxidant
capacity,
low-molecular-weight
thiols,
protein
sulfhydryls,
activity
Mn/Fe
superoxide
dismutases,
azide-insensitive
catalase/peroxidase
measured.
Both
univariate
multivariate
models
analyzing
biomarkers
indicate
significant
disturbances
balance
are
present.
findings
demonstrate
motor
impairment
observed
can
occur
without
concurrent
imbalances
system.
Biosensors,
Journal Year:
2022,
Volume and Issue:
12(1), P. 41 - 41
Published: Jan. 14, 2022
Although
iron
is
an
essential
constituent
for
almost
all
living
organisms,
dyshomeostasis
at
a
cellular
level
may
trigger
oxidative
stress
and
neuronal
damage.
Hence,
there
are
numerous
reported
carbon
dots
(CDs)
that
have
been
synthesized
applied
to
determine
intracellular
ions.
However,
among
CDs
focused
detect
Fe3+
ions,
only
few
designed
specifically
Fe2+
ions
over
monitoring
of
We
developed
the
nitrogen-doped
(NCDs)
fluorescence
turn-off
detection
level.
The
as-synthesized
NCDs
exhibit
strong
blue
low
cytotoxicity,
acting
as
probes
0.702
µM
in
aqueous
solution
within
2
min
visualize
concentration
range
from
0
500
20
min.
as-prepared
possess
some
advantages
such
high
biocompatibility,
properties,
selectivity,
rapidity
monitoring,
making
excellent
nanoprobe
biosensing
ferrous
Journal of Neural Transmission,
Journal Year:
2022,
Volume and Issue:
129(10), P. 1257 - 1270
Published: July 19, 2022
Abstract
Neuromelanin
is
a
black-brownish
pigment,
present
in
so-called
neuromelanin
granules
(NMGs)
the
cell
bodies
of
dopaminergic
neurons
substantia
nigra
(SN)
pars
compacta
.
These
are
lost
neurodegenerative
diseases,
such
as
Parkinson’s
disease
and
dementia
with
Lewy
bodies.
Although
it
known
that
lipids,
proteins,
environmental
toxins
accumulate
NMGs,
function
NMGs
has
not
yet
been
finally
clarified
well
their
origin
synthesis
neuromelanin.
We,
therefore,
isolated
surrounding
SN
tissue
from
control
patients
by
laser
microdissection
analyzed
proteomic
profile
tandem
mass
spectrometry.
With
our
improved
workflow,
we
were
able
to
(1)
strengthen
regularly
reported
link
between
lysosomes,
(2)
detect
tyrosine
hydroxylase
be
highly
abundant
which
may
related
(3)
indicate
undescribed
stress
(SGs)
NMGs.
Based
on
findings,
cautiously
hypothesize,
SGs
or
form
close
proximity
them,
potentially
due
oxidative
caused
neuromelanin-bound
metals.
