Cellular pathways of hereditary spastic paraplegia

Annu Rev Neurosci. 2012:35:25-47. doi: 10.1146/annurev-neuro-062111-150400. Epub 2012 Apr 20.


Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticulum, as well as intracellular membrane trafficking and distribution as primary defects underlying the HSPs, with clear relevance for other long axonopathies affecting peripheral nerves and lower motor neurons.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / physiology
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / physiology
  • Humans
  • Models, Neurological
  • Nerve Fibers, Myelinated / physiology*
  • Nervous System Diseases / genetics
  • Nervous System Diseases / physiopathology
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Protein Transport / genetics
  • Protein Transport / physiology
  • Pyramidal Tracts / growth & development
  • Pyramidal Tracts / physiology*
  • Spastic Paraplegia, Hereditary / genetics
  • Spastic Paraplegia, Hereditary / physiopathology*


  • Bone Morphogenetic Proteins