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| Status |
Public on Oct 06, 2021 |
| Title |
The LRRK2 G2019S mutation alters astrocyte-to-neuron communication via extracellular vesicles and induces neuron atrophy in a human iPSC-derived model of Parkinson’s disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Astrocytes are essential cells of the central nervous system, characterized by dynamic relationships with neurons that range from functional metabolic interactions and regulation of neuronal firing activities, to the release of neurotrophic and neuroprotective factors. In Parkinson’s disease (PD), dopaminergic neurons are a vulnerable population progressively lost during the course of the disease, but the effects of PD on astrocytes and astrocyte-to-neuron communication remains mostly unknown. This study focuses on the effects of the PD-related mutation LRRK2 G2019S in astrocytes, using patient-derived induced pluripotent stem cells. We report the alteration of extracellular vesicle (EV) biogenesis in astrocytes, and we identify the abnormal accumulation of key PD-related proteins within multi vesicular bodies (MVBs). We found that dopaminergic neurons internalize astrocyte-secreted EVs but LRRK2 G2019S EVs are abnormally enriched in the neurites and provide only marginal neurotrophic support to dopaminergic neurons. Thus, dysfunctional astrocyte-to-neuron communication via altered EV biological properties could participate in the progression of PD.
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| Overall design |
Differential gene expression between wild-type and LRRK2 G2019S iPSC-derived astrocytes.
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| Contributor(s) |
O'Shea EK, de Rus Jacquet A, Tancredi JL, Lemire AL, DeSantis MC, Li W |
| Citation(s) |
34590578 |
| Submission date |
Jun 18, 2020 |
| Last update date |
Jan 05, 2022 |
| Contact name |
Aurelie de Rus Jacquet |
| E-mail(s) |
aurelie.jacquet@crchudequebec.ulaval.ca
|
| Phone |
5813974933
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| Organization name |
Universite Laval
|
| Street address |
2705 Boulevard Laurier
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| City |
Quebec |
| State/province |
QC |
| ZIP/Postal code |
G1V 4G2 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA640370 |
| SRA |
SRP267856 |
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