Characterization of an ATP13A2 Knockout Zebrafish Model of Neurodegeneration

ATP13A2 is a lysosomal P5-type ATPase whose loss-of-function mutations are associated with several neurodegenerative disorders, including Kufor-Rakeb syndrome, neuronal ceroid lipofuscinosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis-like phenotypes. Although ATP13A2 has been linked to lysosomal homeostasis and intracellular trafficking, the mechanisms underlying its role in neurodegeneration are still not completely understood. The aim of this thesis is to characterize a new ATP13A2 knockout zebrafish (Danio rerio) model in order to investigate the effects of ATP13A2 deficiency during development and adulthood. The study includes morphological, behavioral and molecular analyses to identify phenotypic alterations associated with the loss of ATP13A2 and to evaluate their relationship with lysosomal dysfunction and neurodegeneration. Overall, this work will contribute to the characterization of a new in vivo model for the study of ATP13A2-related disorders and provide a valuable platform for future drug screening and preclinical evaluation of potential therapeutic strategies.