Hereditary spastic paraplegia: investigations on the regulation of spastin protein mediated by the kinase HIPK2 in proliferating cells and in neurons

Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders characterized by progressive spasticity of the lower extremities, due to degeneration of cortico-spinal neurons. The common type is due to mutations in spastin, a protein involved in cellular division and in intracellular transport. Several studies show that it is crucial to have the right amount of spastin in cells. Curative therapies and approaches to manage HSP progression are completely lacking. However, recent findings indicates that restoring the proper protein levels of spastin might be beneficial for patients with spastin-deficient HSP. Thus, in order to develop therapeutic approaches, it is crucial to study in detail the mechanisms regulating spastin protein levels. Recently, we have identified a new regulator of spastin protein levels: the protein kinase HIPK2. The aim of this project is to deeply investigate how HIPK2 regulates spastin. This study will provide potentially useful tools to increase the dosage of spastin and preliminary studies will be also conducted on cells derived from patients.