Therapeutic Strategies for Mutant <i>SPAST</i>-Based Hereditary Spastic Paraplegia

Abstract

Mutations of the SPAST gene that encodes the microtubule-severing enzyme called spastin are the chief cause of Hereditary Spastic Paraplegia. Growing evidence indicates that pathogenic mutations functionally compromise the spastin protein and endow it with toxic gain-of-function properties. With each of these two factors potentially relevant to disease etiology, the present article discusses possible therapeutic strategies that may ameliorate symptoms in patients suffering from SPAST-based Hereditary Spastic Paraplegia, which is usually termed SPG4-HSP.

Keywords

• Hereditary Spastic Paraplegia
• spastin
• <i>SPAST</i>
• microtubule
• <i>SPG4</i>-HSP
• haploinsufficiency