Translational Neurodegeneration,
Год журнала:
2023,
Номер
12(1)
Опубликована: Дек. 15, 2023
Parkinson's
disease
(PD)
is
one
of
the
most
prevalent
neurodegenerative
diseases.
The
typical
symptomatology
PD
includes
motor
symptoms;
however,
a
range
nonmotor
symptoms,
such
as
intestinal
issues,
usually
occur
before
symptoms.
Various
microorganisms
inhabiting
gastrointestinal
tract
can
profoundly
influence
physiopathology
central
nervous
system
through
neurological,
endocrine,
and
immune
pathways
involved
in
microbiota-gut-brain
axis.
In
addition,
extensive
evidence
suggests
that
gut
microbiota
strongly
associated
with
PD.
This
review
summarizes
latest
findings
on
microbial
changes
their
clinical
relevance,
describes
underlying
mechanisms
which
bacteria
may
mediate
PD,
discusses
correlations
between
microbes
anti-PD
drugs.
this
outlines
status
research
therapies
for
future
directions
PD-gut
research.
Parkinsonism & Related Disorders,
Год журнала:
2024,
Номер
122, С. 106101 - 106101
Опубликована: Март 15, 2024
We
recently
proposed
a
new
disease
model
of
Parkinson's
–
the
-Synuclein
Origin
site
and
Connectome
model.
The
posits
that
initial
pathology
starts
either
in
olfactory
bulb
or
amygdala
leading
to
brain-first
subtype,
enteric
nervous
system
body-first
subtype.
These
subtypes
should
be
distinguishable
early
course
on
range
imaging,
clinical,
neuropathological
markers.
Here,
we
review
recent
original
human
studies,
which
tested
predictions
model.Molecular
imaging
studies
were
generally
agreement
with
model,
whereas
structural
such
as
MRI
volumetry,
showed
conflicting
findings.
Most
large-scale
clinical
supportive,
reporting
clustering
relevant
markers
including
REM-sleep
behavior
disorder,
constipation,
autonomic
dysfunction,
neuropsychiatric
symptoms,
cognitive
impairment.
Finally,
-synuclein
deposition
antemortem
postmortem
tissues
revealed
distribution
pathology,
supports
Journal of Parkinson s Disease,
Год журнала:
2024,
Номер
14(3), С. 383 - 397
Опубликована: Апрель 16, 2024
The
question
whether
Parkinson’s
disease
dementia
(PDD)
and
with
Lewy
bodies
(DLB)
are
expressions
of
the
same
underlying
has
been
vigorously
debated
for
decades.
recently
proposed
biological
definitions
body
disease,
which
do
not
assign
any
particular
importance
to
dopamine
system
over
other
degenerating
neurotransmitter
systems,
once
more
brought
discussion
about
different
types
forefront.
Here,
we
briefly
compare
PDD
DLB
in
terms
their
symptoms,
imaging
findings,
neuropathology,
ultimately
finding
them
be
indistinguishable.
We
then
present
a
conceptual
framework
demonstrate
how
one
can
view
clinical
syndromes
as
manifestations
shared
disease.
Early
isolated
RBD,
pure
autonomic
failure
perhaps
even
psychiatric
represent
diverse
initial
stages
They
characterized
by
heterogeneous
comparatively
limited
neuronal
dysfunction
damage.
In
contrast,
dementia,
an
encompassing
term
both
DLB,
represents
uniform
advanced
stage
Patients
this
category
display
extensive
severe
pathology,
frequently
accompanied
co-existing
pathologies,
well
multi-system
degeneration.
Thus,
propose
that
should
viewed
single
entity.
Phenotypic
variance
is
caused
presence
individual
risk
factors,
mechanisms,
co-pathologies.
Distinct
subtypes
therefore
defined
subtype-specific
mechanisms
or
biomarkers.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июнь 15, 2024
Lewy
body
(LB)
diseases,
characterized
by
the
aggregation
of
misfolded
α-synuclein
proteins,
exhibit
notable
clinical
heterogeneity.
This
may
be
due
to
variations
in
accumulation
patterns
LB
neuropathology.
Here
we
apply
a
data-driven
disease
progression
model
regional
neuropathological
density
scores
from
814
brain
donors
with
pathology.
We
describe
three
inferred
trajectories
pathology
that
are
differing
clinicopathological
presentation
and
longitudinal
antemortem
progression.
Most
(81.9%)
show
earliest
olfactory
bulb,
followed
either
limbic
(60.8%)
or
brainstem
(21.1%)
regions.
The
remaining
(18.1%)
initially
abnormalities
Early
is
associated
Alzheimer's
disease-associated
characteristics
while
early
progressive
motor
impairment
substantial
outside
brain.
Our
data
provides
evidence
for
heterogeneity
temporal
spread
pathology,
possibly
explaining
some
disparities
observed
disease.
Journal of Clinical Neurology,
Год журнала:
2025,
Номер
21(1), С. 21 - 21
Опубликована: Янв. 1, 2025
Parkinson's
disease
(PD)
is
characterized
by
various
prodromal
symptoms,
and
these
symptoms
are
mostly
investigated
retrospectively.
While
some
such
as
rapid
eye
movement
sleep
behavior
disorder
highly
specific,
others
common.
This
makes
it
challenging
to
predict
those
at
risk
of
PD
based
solely
on
less-specific
symptoms.
The
prediction
accuracy
when
using
only
can
be
improved
analyzing
the
vast
amount
information
available
sophisticated
deep-learning
techniques.
study
aimed
improve
performance
deep-learning-based
screening
in
detecting
medical-claims
data,
including
prescription
information.
We
sampled
820
patients
8,200
age-
sex-matched
non-PD
controls
from
Korean
National
Health
Insurance
cohort
data.
A
algorithm
was
developed
combinations
diagnostic
codes,
medication
periods.
During
period
year
-3
0,
predicting
codes
yielded
a
high
0.937.
Adding
for
same
did
not
increase
(0.931-0.935).
For
earlier
(year
-6
-3),
decreased
0.890
codes.
inclusion
all
medication-codes
data
increased
that
markedly
0.922.
both
effective
PD.
Developing
surveillance
system
with
automatically
collected
developing
could
cost-effective.
approach
streamline
process
disease-modifying
drugs
focusing
most-appropriate
candidates
accurate
tests.
Neuropathology and Applied Neurobiology,
Год журнала:
2024,
Номер
50(1)
Опубликована: Фев. 1, 2024
Abstract
Aims
According
to
Braak's
hypothesis,
it
is
plausible
that
Parkinson's
disease
(PD)
originates
in
the
enteric
nervous
system
(ENS)
and
spreads
brain
through
vagus
nerve.
In
this
work,
we
studied
whether
inflammatory
bowel
diseases
(IBDs)
humans
can
progress
with
emergence
of
pathogenic
α‐synuclein
(α‐syn)
gastrointestinal
tract
midbrain
dopaminergic
neurons.
Methods
We
have
analysed
gut
ventral
from
subjects
previously
diagnosed
IBD
form
a
DSS‐based
rat
model
inflammation
terms
α‐syn
pathology.
Results
Our
data
support
existence
both
brain,
thus
reinforcing
potential
role
ENS
as
contributing
factor
PD
aetiology.
Additionally,
effect
demonstrate
(i)
appearance
P‐α‐syn
inclusions
Auerbach's
Meissner's
plexuses
(gut),
(ii)
an
increase
expression
mesencephalon
(brain)
(iii)
degeneration
nigral
neurons,
which
all
are
considered
classical
hallmarks
PD.
Conclusion
These
results
strongly
plausibility
hypothesis
emphasise
significance
peripheral
gut‐brain
axis
initiating
aggregation
transport
substantia
nigra,
resulting
neurodegeneration.
npj Parkinson s Disease,
Год журнала:
2024,
Номер
10(1)
Опубликована: Март 19, 2024
Parkinson's
disease
(PD)
is
the
second
most
common
neurodegenerative
worldwide
and
presents
pathologically
with
Lewy
pathology
dopaminergic
neurodegeneration.
contains
aggregated
α-synuclein
(αSyn),
a
protein
encoded
by
SNCA
gene
which
also
mutated
or
duplicated
in
subset
of
familial
PD
cases.
Due
to
its
predominant
presynaptic
localization,
immunostaining
for
results
diffuse
reactivity
pattern,
providing
little
insight
into
types
cells
expressing
αSyn.
As
result,
αSyn
expression-driven
cellular
vulnerability
has
been
difficult
ascertain.
Using
combination
knock-in
mice
that
target
nucleus
(Snca
Brain,
Год журнала:
2024,
Номер
147(7), С. 2308 - 2324
Опубликована: Фев. 29, 2024
Cholinergic
degeneration
is
significant
in
Lewy
body
disease,
including
Parkinson's
dementia
with
bodies,
and
isolated
REM
sleep
behaviour
disorder.
Extensive
research
has
demonstrated
cholinergic
alterations
the
CNS
of
these
disorders.
More
recently,
studies
have
revealed
denervation
organs
that
receive
parasympathetic
denervation.
This
enables
a
comprehensive
review
changes
encompassing
both
central
peripheral
regions,
various
disease
stages
diagnostic
categories.
Across
studies,
brain
regions
affected
show
equal
or
greater
levels
impairment
compared
to
without
dementia.
observation
suggests
continuum
between
Patients
exhibit
relative
sparing
limbic
whereas
occipital
superior
temporal
appear
be
similar
extent
patients
implies
posterior
cell
groups
basal
forebrain
are
early
disorders,
while
more
anterior
typically
later
progression.
The
topographical
observed
by
comorbid
Alzheimer
pathology
may
reflect
combination
seen
pure
forms
those
Alzheimer's
disease.
co-pathology
important
understand
Thalamic
innervation
dementia,
this
contribute
distinct
clinical
presentations
groups.
In
thalamus
variably
affected,
suggesting
different
sequential
involvement
disorder
demonstrate
abdominal
from
dorsal
motor
nucleus
vagus,
who
experienced
their
prodrome.
for
understanding
prodromal
manifest
phases
conclusion,
carry
implications
phenotypes
influence
co-pathology,
delineating
subtypes
pathological
spreading
routes,
developing
tailored
treatments
targeting
system.
Journal of Parkinson s Disease,
Год журнала:
2024,
Номер
14(3), С. 363 - 381
Опубликована: Апрель 9, 2024
The
brain-
and
body-first
models
of
Lewy
body
disorders
predict
that
aggregated
alpha-synuclein
pathology
usually
begins
in
either
the
olfactory
system
or
enteric
nervous
system.
In
both
scenarios
seems
to
arise
structures
are
closely
connected
outside
world.
Environmental
toxicants,
including
certain
pesticides,
industrial
chemicals,
air
pollution
therefore
plausible
trigger
mechanisms
for
Parkinson’s
disease
dementia
with
bodies.
Here,
we
propose
toxicants
inhaled
through
nose
can
lead
pathological
changes
subsequently
spread
give
rise
a
brain-first
subtype
disease.
Similarly,
ingested
pass
gut
cause
then
extends
via
parasympathetic
sympathetic
pathways
ultimately
produce
subtype.
resulting
be
tracked
by
development
symptoms,
clinical
assessments,
vivo
imaging,
examination.
integration
environmental
exposures
into
generates
testable
hypotheses,
on
prevalence
conditions,
their
future
incidence,
imaging
patterns,
signatures.
proposed
link,
though,
has
limitations
leaves
many
questions
unanswered,
such
as
role
skin,
influence
microbiome,
effects
ongoing
exposures.
Despite
these
limitations,
interaction
exogenous
factors
may
explain
mysteries
open
door
toward
ultimate
goal
–prevention.
