bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 31, 2024
Abstract
Chronic
olfactory
dysfunction
can
be
associated
with
parkinsonism,
dementia,
demyelinating
disorders
and
schizophrenia.
The
epithelium
(OE)
represents
an
interface
between
the
environment
central
nervous
system.
Mounting
evidence
implicates
environmental
factors
in
neurodegenerative
disease
processes,
necessitating
investigations
into
their
interactions
host’s
genome.
In
Parkinson
disease,
hyposmia
often
precedes
motor
symptoms,
raising
possibility
that
OE
could
involved
initiation.
We
previously
demonstrated
abundant
α-synuclein
expression
mammalian
as
well
aggregate
formation
nerve.
Current
vitro
models
of
are
limited,
relying
primarily
on
post-mitotic
cultures
established
from
biopsies.
To
address
this
gap,
we
present
a
method
for
generating
organoids
adult
mice.
These
comprise
neuronal
non-neuronal
cell
types,
including
sustentacular
cells,
thus
encompassing
structural
elements
situ
.
Expression
sensory
neuron
marker
OMP
Parkinson’s-linked
was
also
detected
organoids,
highlighting
potential
usefulness
to
mechanistic
research.
were
kept
culture
up
3
weeks.
addition,
inoculated
neurotropic
vesicular
stomatitis
virus
model
infections.
conclude
organoid
system
offers
new
platform
studying
airborne
genetically
defined
host;
this,
study
biology
enable
exploration
processes
within
tissue.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июль 18, 2023
The
nuclear
receptor,
Nurr1,
is
critical
for
both
the
development
and
maintenance
of
midbrain
dopamine
neurons,
representing
a
promising
molecular
target
Parkinson's
disease
(PD).
We
previously
identified
three
Nurr1
agonists
(amodiaquine,
chloroquine
glafenine)
that
share
an
identical
chemical
scaffold,
4-amino-7-chloroquinoline
(4A7C),
suggesting
structure-activity
relationship.
Herein
we
report
systematic
medicinal
chemistry
search
in
which
over
570
4A7C-derivatives
were
generated
characterized.
Multiple
compounds
enhance
Nurr1's
transcriptional
activity,
leading
to
identification
optimized,
brain-penetrant
agonist,
4A7C-301,
exhibits
robust
neuroprotective
effects
vitro.
In
addition,
4A7C-301
protects
neurons
MPTP-induced
male
mouse
model
PD
improves
motor
non-motor
olfactory
deficits
without
dyskinesia-like
behaviors.
Furthermore,
significantly
ameliorates
neuropathological
abnormalities
dysfunctions
AAV2-mediated
α-synuclein-overexpressing
models.
These
disease-modifying
properties
may
warrant
clinical
evaluation
this
or
analogous
treatment
patients
with
PD.
Progress in Neurobiology,
Год журнала:
2023,
Номер
228, С. 102486 - 102486
Опубликована: Июнь 19, 2023
Olfaction
is
an
important
sensory
modality
for
many
species
and
greatly
influences
animal
human
behavior.
Still,
much
about
olfactory
perception
remains
unknown.
The
anterior
nucleus
one
of
the
brain's
central
early
processing
areas.
Located
directly
posterior
to
bulb
in
peduncle
with
extensive
in-
output
connections
unique
cellular
composition,
it
connects
centers
left
right
hemispheres.
Almost
20
years
have
passed
since
last
comprehensive
review
on
has
been
published
significant
advances
regarding
its
anatomy,
function,
pathophysiology
made
meantime.
Here
we
briefly
summarize
previous
knowledge
nucleus,
give
detailed
insights
into
progress
that
recent
years,
map
out
emerging
importance
translational
research
neurological
diseases.
Olfactory
dysfunction
is
among
the
earliest
non-motor
symptoms
of
Parkinson's
disease
(PD).
As
foremost
pathological
hallmark,
α-synuclein
initiates
pathology
in
olfactory
pathway
at
early
stage
PD,
particularly
epithelium
(OE)
and
bulb
(OB).
However,
local
neural
microcircuit
mechanisms
underlying
between
OE
OB
PD
remain
unknown.We
observed
that
odor
detection
discrimination
were
impaired
6-month-old
SNCA-A53T
mice,
while
their
motor
ability
remained
unaffected.
It
was
confirmed
increased
accumulated
but
not
OE.
Notably,
hyperactivity
mitral/tufted
cells
excitation/inhibition
imbalance
found
which
attributed
to
GABAergic
transmission
aberrant
expression
GABA
transporter
1
vesicular
OB.
We
further
showed
tiagabine,
a
potent
selective
reuptake
inhibitor,
could
reverse
function
signaling
mice.Taken
together,
our
findings
demonstrate
potential
synaptic
PD.
These
results
highlight
critical
role
diagnosis
provide
therapeutic
strategy
for
early-stage
Proteomes,
Год журнала:
2024,
Номер
12(1), С. 9 - 9
Опубликована: Март 21, 2024
Background:
Very
little
is
known
about
the
proteome
of
human
olfactory
system
and
how
diseases
associated
with
dysfunctions
can
affect
it.
With
this
review,
we
try
to
summarize
existing
literature
on
use
technique
for
a
better
understanding
neurodegenerative
disease
process.
Methods:
We
used
PubMed
database
found
different
articles
which
were
then
selected
independently
by
three
authors.
Results:
157
articles,
which,
after
careful
selection,
only
30
analyzed
in
review.
presented
all
associations
identified
between
protein/pathway
alterations
SARS-CoV-2
infection.
Conclusions:
think
that
through
blood,
saliva,
mucus
analysis
could
be
new
way
understand,
diagnose,
finally
treat
diseases.
Ageing and Neurodegenerative Diseases,
Год журнала:
2025,
Номер
5(1)
Опубликована: Янв. 26, 2025
With
aging,
neural
stem
cells
(NSCs)
undergo
age-related
changes,
including
metabolic
abnormalities,
disrupted
protein
homeostasis,
mitochondrial
dysfunction,
reduced
genetic
stability,
and
more
notably,
a
diminished
capacity
for
proliferation
differentiation.
These
changes
may
contribute
to
the
development
of
neurodegenerative
diseases
such
as
Alzheimer’s
disease
(AD)
Parkinson’s
(PD).
In
these
conditions,
disease-specific
pathological
interact
with
alterations
NSCs,
resulting
in
impairment
neurogenesis,
which
further
leads
cognitive,
mood,
motor
decline.
Based
on
potential
therapeutics
targeting
neurogenesis
cell-based
therapies
restore
functions
NSCs
replace
degenerated
neurons,
aiming
ameliorate
functional
decline
diseases.
While
therapies,
cell
transplantation
secretome
therapy,
show
great
treatment
diseases,
challenges
tumorigenesis,
immune
rejection,
extraction
or
storage
need
be
addressed.
A
better
understanding
age-
disease-related
underlying
mechanism
driving
benefits
drawbacks
therapeutic
approaches
provide
insights
novel
disease-modifying
interventions
future
Cells,
Год журнала:
2025,
Номер
14(5), С. 347 - 347
Опубликована: Фев. 27, 2025
Neurodegenerative
diseases
encompass
a
number
of
very
heterogeneous
disorders,
primarily
characterized
by
neuronal
loss
and
concomitant
decline
in
neurological
function.
Examples
this
type
clinical
condition
are
Alzheimer's
Disease,
Parkinson's
Huntington's
Disease
Amyotrophic
Lateral
Sclerosis.
Age
has
been
identified
as
major
risk
the
etiology
these
which
explains
their
increased
incidence
developed
countries.
Unfortunately,
despite
continued
intensive
efforts,
no
cure
yet
found
for
any
diseases;
reliable
markers
that
allow
an
early
diagnosis
disease
identification
key
molecular
events
leading
to
onset
progression
lacking.
Altered
adult
neurogenesis
appears
precede
appearance
severe
symptoms.
Given
scarcity
human
samples
considerable
differences
with
model
species,
increasingly
complex
stem-cell-based
models
being
developed.
These
shedding
light
on
alterations
contribute
development,
facilitating
new
targets
providing
screening
platform
testing
candidate
drugs.
Moreover,
secretome
other
promising
features
cell
types
explored,
use
them
replacement
cells
high
plasticity
or
co-adjuvant
therapy
combinatorial
treatments.
