Hereditary spastic paraplegias (HSPs) are genetic conditions characterized by weakness and spasticity of the lower limbs, owing to a progressive length-dependent distal axonopathy, mainly affecting the lateral corticospinal tracts. HSPs are genetically heterogeneous. Despite the molecular complexity of HSPs, common pathogenic themes are emerging from functional studies of the genes. Proteins encoded by HSP genes are involved in intracellular membrane trafficking, mitochondrial quality control, lipid metabolism, and axonal-myelin interactions. These pathways are required for maintenance of the long corticospinal axons, which in humans can reach the length of 1. m and contain 99% of the cytoplasm of the cell.
Rugarli, E. I. (2013). Spastic Paraplegia. In Encyclopedia of Biological Chemistry: Second Edition (pp. 267–272). Elsevier Inc. https://doi.org/10.1016/B978-0-12-378630-2.00299-1