International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(7), P. 6312 - 6312
Published: March 28, 2023
The
self-association
of
amylogenic
proteins
to
the
fibril
form
is
considered
a
pivotal
factor
in
pathogenesis
neurodegenerative
diseases,
including
Parkinson's
disease
(PD).
PD
causes
unintended
or
uncontrollable
movements
its
common
symptoms.
α-synuclein
major
cause
development
and
thus
has
been
main
target
numerous
studies
suppress
sequester
expression
effectively
degrade
it.
Nonetheless,
date,
there
are
no
efficient
proven
ways
prevent
pathological
protein
aggregation.
Recent
investigations
proposed
applying
an
external
electric
field
interrupt
fibrils.
This
method
non-invasive
approach
that
certain
benefit
over
others.
We
performed
molecular
dynamics
(MD)
simulations
by
on
highly
toxic
fibrils
gain
molecular-level
insight
into
disruption
mechanisms.
results
revealed
applied
induces
substantial
changes
conformation
Furthermore,
we
show
threshold
value
for
strength
required
completely
disrupt
opening
hydrophobic
core
fibril.
Thus,
our
findings
might
serve
as
valuable
foundation
better
understand
mechanisms
disaggregation
process
under
field.
Analytical Chemistry,
Journal Year:
2024,
Volume and Issue:
96(15), P. 6021 - 6029
Published: April 1, 2024
Sensitive
analytical
techniques
that
are
capable
of
detecting
and
quantifying
disease-associated
biomolecules
indispensable
in
our
efforts
to
understand
disease
mechanisms
guide
therapeutic
intervention
through
early
detection,
accurate
diagnosis,
effective
monitoring
disease.
Parkinson's
Disease
(PD),
for
example,
is
one
the
most
prominent
neurodegenerative
disorders
world,
but
diagnosis
PD
has
primarily
been
based
on
observation
clinical
symptoms.
The
protein
α-synuclein
(α-syn)
emerged
as
a
promising
biomarker
candidate
PD,
lack
methods
measure
complex
variants
α-syn
prevented
its
widespread
use
biomarker.
Antibody-based
such
immunoassays
mass
spectrometry-based
approaches
have
used
limited
number
forms;
however,
these
fail
differentiate
display
subtle
differences
only
sequence
structure.
In
this
work,
we
developed
cyclic
ion
mobility-mass
spectrometry
method
combines
multiple
stages
activation
timed
selection
quantify
using
both
mass-
structure-based
measurements.
This
can
allow
quantification
several
present
at
physiological
levels
biological
fluid.
Taken
together,
approach
be
galvanize
future
aimed
understanding
underlying
serves
starting
point
development
protein-structure-based
diagnostics
interventions.
Journal of Molecular Biology,
Journal Year:
2022,
Volume and Issue:
435(12), P. 167930 - 167930
Published: Dec. 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
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(7), P. 6312 - 6312
Published: March 28, 2023
The
self-association
of
amylogenic
proteins
to
the
fibril
form
is
considered
a
pivotal
factor
in
pathogenesis
neurodegenerative
diseases,
including
Parkinson's
disease
(PD).
PD
causes
unintended
or
uncontrollable
movements
its
common
symptoms.
α-synuclein
major
cause
development
and
thus
has
been
main
target
numerous
studies
suppress
sequester
expression
effectively
degrade
it.
Nonetheless,
date,
there
are
no
efficient
proven
ways
prevent
pathological
protein
aggregation.
Recent
investigations
proposed
applying
an
external
electric
field
interrupt
fibrils.
This
method
non-invasive
approach
that
certain
benefit
over
others.
We
performed
molecular
dynamics
(MD)
simulations
by
on
highly
toxic
fibrils
gain
molecular-level
insight
into
disruption
mechanisms.
results
revealed
applied
induces
substantial
changes
conformation
Furthermore,
we
show
threshold
value
for
strength
required
completely
disrupt
opening
hydrophobic
core
fibril.
Thus,
our
findings
might
serve
as
valuable
foundation
better
understand
mechanisms
disaggregation
process
under
field.
