Molecular genetics of monogenic movement disorders: making meaning of rare variants

Parkinson's disease (PD) and Spinocerebellar ataxia (SCA) are two age-related neurodegenerative disease that affect the movement of patients. A curative treatment does not exist for both diseases as the molecular mechanisms remain unclear. For a subset of PD cases and all SCA cases, the disease is caused by pathogenic variants in certain genes. Therefore, studying these variants provides molecular insights in the disease mechanisms. Specifically, using a toolbox of molecular techniques, including CRISPR-Cas9 gene-editing, we investigated genetic variants that are linked to SCA and PD to increase our understanding of these variants and the associated defective cellular pathways. We showed that the variants linked to PD cause defects in different pathways involving the removal of cellular waste products, such as the endolysosomal system and mitophagy. Furthermore, we made observations that hint to developmental defects in SCA. Together, we made some meaning of the molecular mechanisms underlying two monogenic movement disorders.

Dissertation: http://hdl.handle.net/11370/385da387-fdb0-4c4a-9e18-98b2b274f04a