HDAC6 in Parkinson's disease

Mutations in LRRK2 are the most common cause of dominantly inherited Parkinson’s disease. LRRK2 is a multi-domain protein with both GTPase and kinase activities that has been shown to affect various cellular processes including axonal transport and autophagy.  

We have previously shown that mutations in the Roc-COR domain of LRRK2 (R1441C and Y1699C) correlate with reduced microtubule acetylation, inhibition of axonal transport and locomotor deficits in Drosophila. Restoring microtubule acetylation by inhibition of the histone deacetylase HDAC6 fully reversed these defects (Godena et al., Nat. Commun., 2014). Together with the increased microtubule acetylation in LRRK2 deficient cells these observations suggested that a physiological role of LRRK2 might be to regulate HDAC6 activity and that this function may be involved in Parkinson’s disease.

In this presentation, I will give an overview of our work on LRRK2-related PD and explore the role of HDAC6.

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