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Funded Studies

Control of Astrocyte Function by LRRK2

Study Rationale:
Mutations in the LRRK2 gene are known to cause Parkinson’s disease (PD), but how mutations in this gene lead to neuron death is not yet known. Astrocytes, which are brain cells that support neuronal survival and actively participate in many aspects of brain function, produce high levels of LRRK2. Disruption of astrocyte-neuron interactions is well-documented in PD; however, whether astrocyte dysfunction directly contributes to PD is unknown. In our studies, we have identified important functions for LRRK2 in controlling the communication between astrocytes and neurons. Moreover, we found evidence that the most common PD-associated LRRK2 mutation impairs key astrocyte functions.

We hypothesize that LRRK2 signaling in astrocytes controls critical aspects of astrocytes’ ability to participate in neuron maturation and synapse development, and that a LRRK2 mutation will disrupt these essential processes.

Study Design:
We will investigate the function of LRRK2 in astrocyte-neuron communication primarily by studying astrocytes and neurons grown in a dish. Specifically, we will compare astrocytes from models with and without a LRRK2 mutation. We will also study human astrocytes and neurons derived from patients who have a LRRK2 mutation.  These experiments will allow us to determine how LRRK2 contributes to astrocyte function and astrocyte-regulated neuron development.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
The results of our studies are poised to provide novel insights into the role of astrocyte dysfunction in PD and identify specific molecules to be targeted with drugs to block disease onset and/or progression.

Next Steps for Development:
The molecular players we identify in our studies may provide druggable targets to block the progression of PD and help repair the functions of astrocytes that are disrupted during PD. Next steps would be around further characterizing those targets.


  • Cagla Eroglu, PhD

    Durham, NC United States

  • Albert La Spada, MD, PhD

    Durham, NC United States

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