Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson’s disease model triggered by α-synuclein overexpression
Zhen Zhang,
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Kun Niu,
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Taoying Huang
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et al.
npj Parkinson s Disease,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Jan. 9, 2025
Chronic
neuroinflammation
with
sustained
microglial
activation
occurs
in
Parkinson's
disease
(PD),
yet
the
mechanisms
and
exact
contribution
of
these
cells
to
neurodegeneration
remains
poorly
understood.
In
this
study,
we
induced
progressive
dopaminergic
neuron
loss
mice
via
rAAV-hSYN
injection
cause
neuronal
expression
α-synuclein,
which
produced
behavioral
alterations.
We
administered
PLX5622,
a
colony-stimulating
factor
1
receptor
inhibitor,
for
3
weeks
prior
injection,
maintaining
it
8
eliminate
microglia.
This
chronic
treatment
paradigm
prevented
development
motor
deficits
concomitantly
preserved
cell
weakened
α-synuclein
phosphorylation.
Gene
profiles
related
extracellular
matrix
(ECM)
remodeling
were
increased
after
microglia
depletion
PD
mice,
further
validated
on
protein
level.
demonstrated
that
exert
adverse
effects
during
α-synuclein-overexpression-induced
lesion
formation,
their
remodels
ECM
aids
recovery
following
insult.
Language: Английский
Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy
Behavioral and Brain Functions,
Journal Year:
2024,
Volume and Issue:
20(1)
Published: Nov. 1, 2024
The
cannabigerol
derivative
VCE-003.2,
which
has
activity
at
the
peroxisome
proliferator-activated
receptor-γ
afforded
neuroprotection
in
experimental
models
of
Parkinson's
disease
(PD)
based
on
mitochondrial
dysfunction
(6-hydroxydopamine-lesioned
mice)
and
neuroinflammation
(LPS-lesioned
mice).
Now,
we
aim
to
explore
VCE-003.2
neuroprotective
properties
a
PD
model
that
also
involves
protein
dysregulation,
other
key
event
pathogenesis.
Language: Английский