Converging Parkinson’s disease pathways: Identification of unique and novel gene dependencies

01/05/2022 to 30/11/2024

Parkinson’s disease (PD) incidence is rising worldwide (Dorsey and Bloem, 2018) but this neurodegenerative disease is currently uncurable. PD is clinically, pathologically and genetically heterogenous with a complex and often multi-factoral underlying biology. Only 10-15% of PD cases are monogenic (caused by a single PD gene mutation, duplication or triplication) and the remaining cases arise sporadically (sporadic or idiopathic PD), although some genetic and environmental risk factors have been identified. Decades of research, mainly utilising genetic PD models has led to the discovery that the build up of insoluble proteins, mitochondrial dysfunction and lysosomal dysfunction can contribute to the underlying pathobiology of PD. Unlike in cancer research (Merck et al. 2020), in PD research there have been no genetic screens (such as CRISPR screens) to identify unique gene dependencies in the development of PD using human neurons.