Drosophila Models of Hereditary Spastic Paraplegia

Book Section

Hereditary spastic paraplegia (HSP) is a debilitating movement disorder with no prevention, no cure, and few options for symptom management. Rapid and relevant information is required, and the model organism Drosophila melanogaster can contribute significantly to our understanding of the cellular mechanisms underlying HSP pathology. We review HSP models based on fly orthologs of spastin, atlastin, reticulon-like 1, spichthyin, spartin, Kinesin heavy chain, swiss cheese, and unexamined causative loci. The relevance of these models to HSP is highlighted by their progressive neurodegeneration with distally increasing severity and impaired locomotor behaviors. Subcellularly, they implicate defects in synapse formation, microtubule regulation, endoplasmic reticulum morphogenesis, membrane trafficking, and axon transport. Much remains to be discovered from these models, including the relationship between these mechanisms. In addition, insights gained from the unique amenability of Drosophila to high-throughput genetic and in vivo pharmacological screens promise to advance our knowledge further and recommend potential therapeutic options.

Full Text

Duke Authors

Cited Authors

  • Ozdowski, EF; Baxter, SL; Sherwood, NT

Published Date

  • January 1, 2015

Book Title

  • Movement Disorders: Genetics and Models: Second Edition

Start / End Page

  • 1103 - 1122

International Standard Book Number 13 (ISBN-13)

  • 9780124051959

Digital Object Identifier (DOI)

  • 10.1016/B978-0-12-405195-9.00073-1

Citation Source

  • Scopus