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allied
academies
Page 45
April 17-18, 2019 | Frankfurt, Germany
Parkinson’s, Huntington’s & Movement Disorders
International Conference on
Journal of Brain and Neurology | Volume 3
Using
Drosophila
to define the role of glia in alpha-Synucleinopathies
Abby L Olsen
Harvard Medical School, USA
α
-synucleinopathies are neurodegenerative
diseases that are characterized pathologically
by α- synuclein inclusions in neurons and glia.
In spite of this, the role of glial α-synuclein
and even glia more broadly in these diseases
is not well understood. Glial α-synuclein may
be of particular importance in multiple system
atrophy (MSA), which is defined pathologically
by glial cytoplasmic α-synuclein inclusions. We
have previously described
Drosophila
models of
neuronal α-synucleinopathy, which recapitulate
key features of the human disorders. We have
now expanded our model to express human
α-synuclein in glia. We demonstrate that
expression of α-synuclein in glia alone results in
α-synuclein aggregation, death of dopaminergic
neurons, impaired locomotor function, and
autonomic dysfunction. Furthermore, co-
expression of α- synuclein in both neurons and
glia worsens these phenotypes as compared to
expression of α- synuclein in neurons alone. We
identify unique transcriptomic signatures induced
by glial as opposed to neuronal α-synuclein.
These results suggest that glial α-synuclein may
contribute to the burden of pathology in the
α-synucleinopathies through a cell type specific
transcriptional program. This new
Drosophila
model system enables further mechanistic
studies dissecting the contribution of glial and
neuronal α-synuclein in vivo, potentially shedding
light on mechanisms of disease that are especially
relevant in MSA but also the α-synucleinopathies
more broadly. Indeed, beyond glial α-synuclein,
we identify additional novel glial modifiers of
neuronal α- synuclein toxicity in the hopes of
eventually turning these modifiers into glial-
based therapeutics for Parkinson’s disease
e
:
alolsen@partners.orgNotes: