Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson’s disease
Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Сен. 12, 2024
Язык: Английский
Mild cognitive impairment in Parkinson's disease: current view
Frontiers in Cognition,
Год журнала:
2024,
Номер
3
Опубликована: Апрель 5, 2024
Parkinson's
disease
(PD),
the
most
common
motor
movement
disorder
and
second
neurodegenerative
after
Alzheimer's
(AD),
is
often
preceded
by
a
period
of
mild
cognitive
impairment
(MCI),
which
associated
with
variety
domains
including
executive
function,
attention,
visuospatial
abilities
memory.
MCI,
risk
factor
for
developing
dementia,
affects
around
30%
de
novo
PD
patients
can
increase
to
75%
more
than
10
years.
While
30–40%
remain
in
MCI
state,
up
60%
will
convert
dementia.
Characteristic
findings
are
slowing
EEG
rhythms,
frontotemporal
hypoperfusion,
decreased
functional
connectivity
default
mode
attentional
networks,
prefrontal
basal-ganglia-cortical
circuits,
manifests
prior
clinical
symptoms
overt
brain
atrophy.
The
heterogeneity
phenotypes
suggests
that
process
multiple
neuronal
networks
neuromodulatory
systems
may
be
superimposed
Lewy
body
Alzheimer's-related
or
other
co-pathologies.
Sparse
neuropathological
data
PD-MCI
revealed
heterogenous
picture
various
morphological
changes
similar
diseases.
This
review
highlights
essential
epidemiological,
clinical,
neuroimaging
PD-MCI,
available
biomarkers,
discusses
pathobiological
mechanisms
involved
its
development.
In
view
complex
pathogenesis,
well-designed
longitudinal
clinico-pathological
studies
warranted
clarify
alterations
leading
PD,
supported
fluid
biomarkers
as
basis
early
diagnosis
future
adequate
treatment
modalities
this
debilitating
disorder.
Язык: Английский
Effects and mechanisms of water extract of Uraria crinit a on manganese chloride-induced apoptosis in SH-SY5Y cells
CyTA - Journal of Food,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 11, 2025
Язык: Английский
Gene therapies for neurogenetic disorders
Trends in Molecular Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3929 - 3929
Опубликована: Апрель 1, 2024
In
the
last
two
decades,
alpha-synuclein
(alpha-syn)
assumed
a
prominent
role
as
major
component
and
seeding
structure
of
Lewy
bodies
(LBs).
This
concept
is
driving
ongoing
research
on
pathophysiology
Parkinson’s
disease
(PD).
line
with
this,
alpha-syn
considered
to
be
guilty
protein
in
process,
it
may
targeted
through
precision
medicine
modify
progression.
Therefore,
designing
specific
tools
block
aggregation
spreading
represents
effort
development
disease-modifying
therapies
PD.
The
present
article
analyzes
concrete
evidence
about
significance
within
LBs.
this
effort,
some
dogmas
are
challenged.
concerns
question
whether
more
abundant
compared
other
proteins
Again,
occurrence
non-protein
constituents
scrutinized.
Finally,
LBs
causing
PD
questioned.
These
revisited
concepts
helpful
process
validating
which
proteins,
organelles,
pathways
likely
involved
damage
meso-striatal
dopamine
neurons
brain
regions
Язык: Английский
Lipids and α-Synuclein: adding further variables to the equation
Frontiers in Molecular Biosciences,
Год журнала:
2024,
Номер
11
Опубликована: Авг. 12, 2024
Graphical
Abstract
The
graphical
abstract
summarises
factors
that
might
lead
to
lipid
changes
and
possible
influences
of
on
synucleinopathies.
Язык: Английский
The GBA1 K198E Variant Is Associated with Suppression of Glucocerebrosidase Activity, Autophagy Impairment, Oxidative Stress, Mitochondrial Damage, and Apoptosis in Skin Fibroblasts
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9220 - 9220
Опубликована: Авг. 25, 2024
Parkinson’s
disease
(PD)
is
a
multifactorial,
chronic,
and
progressive
neurodegenerative
disorder
inducing
movement
alterations
as
result
of
the
loss
dopaminergic
(DAergic)
neurons
pars
compacta
in
substantia
nigra
protein
aggregates
alpha
synuclein
(α-Syn).
Although
its
etiopathology
agent
has
not
yet
been
clearly
established,
environmental
genetic
factors
have
suggested
major
contributors
to
disease.
Mutations
glucosidase
beta
acid
1
(GBA1)
gene,
which
encodes
lysosomal
glucosylceramidase
(GCase)
enzyme,
are
one
risks
for
PD.
We
found
that
GBA1
K198E
fibroblasts
but
WT
showed
reduced
catalytic
activity
heterozygous
mutant
GCase
by
−70%
expression
levels
increased
3.68-fold;
acidification
autophagy
vacuoles
(e.g.,
autophagosomes,
lysosomes,
autolysosomes)
+1600%;
augmented
autophagosome
Beclin-1
(+133%)
LC3-II
(+750%),
lysosomal–autophagosome
fusion
LAMP-2
(+107%);
accumulation
lysosomes
(+400%);
decreased
mitochondrial
membrane
potential
(∆Ψm)
−19%
Parkin
remained
unperturbed;
oxidized
DJ-1Cys106-SOH
+900%,
evidence
oxidative
stress;
phosphorylated
LRRK2
at
Ser935
(+1050%)
along
with
α-synuclein
(α-Syn)
pathological
residue
Ser129
(+1200%);
executer
apoptotic
caspase
3
(cleaved
3)
+733%.
exposure
neutoxin
rotenone
(ROT,
μM)
exacerbated
autophagy–lysosomal
system,
stress,
apoptosis
markers,
ROT
moderately
those
markers
fibroblasts.
concluded
mutation
endogenously
primes
skin
toward
dysfunction,
OS,
apoptosis.
Our
findings
suggest
biochemically
molecularly
equivalent
response
exposed
ROT.
Язык: Английский