Acta Neuropathologica Communications,
Год журнала:
2025,
Номер
13(1)
Опубликована: Фев. 24, 2025
Parkinson's
Disease
(PD)
is
characterized
by
the
aggregation
and
accumulation
of
α-synuclein
(α-syn),
along
with
abnormally
high
levels
α-syn
phosphorylation
at
serine
129
site
(pSer
α-syn,
p-α-syn).
However,
mechanisms
underlying
extensive
in
pathogenesis
PD,
as
well
role
p-α-syn
process,
remain
unclear.
Furthermore,
though
could
bind
to
VAPB
loosen
Endoplasmic
Reticulum
(ER)-mitochondria
associations
disrupting
VAPB-PTPIP51
tethers,
whether
how
regulates
interactions,
remains
Herein,
Co-Immunoprecipitation
Mass
Spectrometry
(CO-IP/MS)
studies
were
preformed
identify
compare
Protein-Protein
Interactions
(PPIs)
phosphorylated
total
midbrains
Thy1-SNCA
transgenic
mice.
We
further
performed
CO-IP
Molecular
Dynamics
(MD)
simulation
assays
confirm
influence
on
aforementioned
interactions.
Additionally,
we
Gene
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
analyses
annotate
functional
features
common
interacting
proteins
VAPB.
The
potential
downstream
verified
via
CO-IP.
According
MD
results,
increased
interacted
directly
PTPIP51.
pathway
enrichment
revealed
that
significantly
involved
protein
binding,
metal
ion
structural
constituent
cytoskeleton,
intermediate
filament
microtubule
organization
processes.
Moreover,
our
findings
confirmed
interactions
target
(CLTC,
CAMK2A,
ATP1A3,
TUBB4B)
These
collectively
elucidate
underpinnings
interaction
between
both
hope
these
will
provide
valuable
insights
into
regulatory
pertinent
diseases.
Parkinsonism & Related Disorders,
Год журнала:
2024,
Номер
122, С. 106077 - 106077
Опубликована: Март 3, 2024
These
facts
argue
against
the
gain-of-function
synucleinopathy
hypothesis,
which
proposes
that
Lewy
pathology
causes
Parkinson's
disease:
(1)
most
brains
from
people
without
neurological
symptoms
have
multiple
pathologies;
(2)
neither
type
nor
distribution
correlate
with
disease
severity
or
progression
in
disease;
(3)
aggregated
α-synuclein
form
of
bodies
is
not
a
space-occupying
lesion
but
insoluble
fraction
its
precursor,
soluble
monomeric
α-synuclein;
(4)
spread
passive,
occurring
by
irreversible
nucleation,
active
replication;
and
(5)
low
cerebrospinal
fluid
levels
predict
brain
atrophy
clinical
progression.
The
transformation
into
may
occur
as
response
to
biological,
toxic,
infectious
stressors
whose
persistence
perpetuates
nucleation
process,
depleting
normal
eventually
leading
neuronal
death.
We
propose
testing
loss-of-function
synucleinopenia
hypothesis
evaluating
neurodegenerative
rescue
effect
replenishing
α-synuclein.
Nature Cell Biology,
Год журнала:
2024,
Номер
26(8), С. 1296 - 1308
Опубликована: Июль 1, 2024
α-Synuclein
(αSYN),
a
pivotal
synaptic
protein
implicated
in
synucleinopathies
such
as
Parkinson's
disease
and
Lewy
body
dementia,
undergoes
phase
separation.
We
reveal
that
vesicle-associated
membrane
2
(VAMP2)
orchestrates
αSYN
separation
both
vitro
cells.
Electrostatic
interactions,
specifically
mediated
by
VAMP2
via
its
juxtamembrane
domain
the
C-terminal
region,
drive
Condensate
formation
is
specific
for
R-SNARE
dependent
on
lipid
binding.
Our
results
delineate
regulatory
mechanism
Furthermore,
we
show
condensates
sequester
vesicles
attract
complexin-1
-2,
thus
supporting
role
physiology
pathophysiology.
Cells,
Год журнала:
2024,
Номер
13(6), С. 474 - 474
Опубликована: Март 7, 2024
Parkinson’s
disease
(PD)
is
a
progressive
neurodegenerative
characterized
by
resting
tremor,
bradykinesia,
rigidity,
and
postural
instability
that
also
includes
non-motor
symptoms
such
as
mood
dysregulation.
Dopamine
(DA)
the
primary
neurotransmitter
involved
in
this
disease,
but
cholinergic
imbalance
has
been
implicated.
Current
intervention
PD
focused
on
replenishing
central
DA,
which
provides
remarkable
temporary
symptomatic
relief
does
not
address
neuronal
loss
progression
of
disease.
It
well
established
nicotinic
receptors
(nAChRs)
can
regulate
DA
release
nicotine
itself
may
have
neuroprotective
effects.
Recent
studies
identified
nAChRs
nonneuronal
cell
types,
including
glial
cells,
where
they
inflammatory
responses.
Given
crucial
role
neuroinflammation
dopaminergic
degeneration
involvement
microglia
astrocytes
response,
provide
novel
therapeutic
target
prevention
and/or
treatment
PD.
In
review,
following
brief
discussion
PD,
we
focus
cells
and,
specifically,
their
pathology
treatment.
Synapsin
and
α-synuclein
represent
a
growing
list
of
condensate-forming
proteins
where
the
material
states
condensates
are
directly
linked
to
cellular
functions
(e.g.,
neurotransmission)
pathology
neurodegeneration).
However,
quantifying
condensate
properties
in
living
systems
has
been
substantial
challenge.
Here,
we
develop
micropipette
aspiration
whole-cell
patch-clamp
(MAPAC),
platform
that
allows
direct
quantification
live
cells.
We
find
10,000-fold
variations
viscoelasticity
synapsin
condensates,
regulated
by
partitioning
α-synuclein,
marker
for
synucleinopathies.
Through
vitro
reconstitutions,
identify
multiple
molecular
factors
distinctly
regulate
viscosity,
interfacial
tension,
maturation
confirming
roles
α-synuclein.
Overall,
our
study
provides
unprecedented
quantitative
insights
into
neuronal
reveals
crucial
role
regulating
viscoelasticity.
Furthermore,
envision
MAPAC
applicable
broad
range
vivo.
Nutrients,
Год журнала:
2024,
Номер
16(13), С. 2041 - 2041
Опубликована: Июнь 27, 2024
With
the
recognition
of
importance
gut-brain
axis
in
Parkinson's
disease
(PD)
etiology,
there
is
increased
interest
developing
therapeutic
strategies
that
target
α-synuclein,
hallmark
abhorrent
protein
PD
pathogenesis,
which
may
originate
gut.
Research
has
demonstrated
inhibiting
aggregation,
oligomerization,
and
fibrillation
α-synuclein
are
key
for
modification.
Polyphenols,
rich
fruits
vegetables,
drawing
attention
their
potential
role
this
context.
In
paper,
we
reviewed
how
polyphenols
influence
composition
functional
capabilities
gut
microbiota
resulting
microbial
metabolites
potentially
enhance
modulation
aggregation.
Understanding
interaction
between
identifying
specific
microbes
efficacy
crucial
precision
nutrition
based
on
microbiome.
Neurochemistry International,
Год журнала:
2024,
Номер
178, С. 105790 - 105790
Опубликована: Июнь 7, 2024
Neurodegenerative
diseases
are
characterized
by
the
progressive
loss
of
neuronal
structure
and
function,
posing
a
tremendous
burden
on
health
systems
worldwide.
Although
underlying
pathological
mechanisms
for
various
neurodegenerative
still
unclear,
common
hallmark
is
abundance
neuroinflammatory
processes,
which
affect
both
disease
onset
progression.
In
this
review,
we
explore
pathways
role
neuroinflammation
in
further
assess
potential
use
curcumin,
natural
spice
with
antioxidant
anti-inflammatory
properties
that
has
been
extensively
used
worldwide
as
traditional
medicine
therapeutic
agent.
Following
examination
preclinical
clinical
studies
assessed
curcumin
agent,
highlight
bioavailability
body
discuss
challenges
benefits
using
compound
treating
neurodegeneration.
elucidating
involvement
aging
neurodegeneration
great
developing
future
CNS-related
targets,
research
required
to
elucidate
Curcumin
affects
brain
physiology,
especially
BBB
integrity,
under
physiological
conditions.
The
cytosolic
proteins
synucleins
and
synapsins
are
thought
to
play
cooperative
roles
in
regulating
synaptic
vesicle
(SV)
recycling,
but
mechanistic
insight
is
lacking.
Here,
we
identify
the
synapsin
E-domain
as
an
essential
functional
binding-partner
of
α-synuclein
(α-syn).
Synapsin
allows
α-syn
functionality,
binds
α-syn,
necessary
sufficient
for
enabling
effects
at
synapses
cultured
mouse
hippocampal
neurons.
Together
with
previous
studies
implicating
clustering
SVs,
our
experiments
advocate
a
role
these
two
maintaining
physiologic
SV
clusters.