Dr Alexander Patto
Cellular and Molecular Neuroscience
SPG11 loss-of-function mutations can cause any of three neurodegenerative diseases, sometimes with different presentations in the same family: a severe form of hereditary spastic paraplegia; a juvenile and slowly progressive ALS; or juvenile Parkinsonism. My goal is to understand the cellular function of SPG11 protein, and the defects that can result when it is absent, using Drosophila as an animal model. SPG11 encodes a large protein called spatacsin, which interacts with proteins in the late endolysosomal/autophagy pathways. SPG11::GFP coats acidic compartments (putatively autolysosomes) in fat body. spg11 loss-of-function mutants show accumulation of p62 protein, an autophagy substrate, with age. Flies also present an increased amount of ATG8a-II, indicative of an autophagy increase, suggesting a possible autophagy overload. This suggests that autophagy defects might contribute to SPG11 mutant pathology in neurodegenerative disease.
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