ABSTRACT
Hereditary spastic paraplegias (HSPs) are a group of hereditary neurological disorders characterised by degeneration of corticospinal tract axons and spasticity of the lower extremities. This chapter attempts to review and assess both the contributions of Drosophila to the field to date, and its potential for future contributions. Behavioural and cellular studies indicate that kinesin plays an important role in maintaining normal axonal transport and neurotransmission in Drosophila. The properties of some HSP genes also point to some aspects of membrane traffic between the plasma membrane, endosomes and lysosomes as a process whose disruption may cause HSP. Mutations in L1-CAM cause an X-linked complicated spastic paraplegia associated with mental retardation, aphasia, shuffling gait, adducted thumbs syndrome, and in X-linked hydrocephalus. The known functions of dynamin superfamily members and the transmembrane domains of atlastin also tentatively suggest a defect in membrane traffic caused by atlastin mutations in HSP, but how this leads to axonal degeneration is unknown.
