Part of the book: Spinocerebellar Ataxia
Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of inherited neurodegenerative diseases with the cardinal feature of a length-dependent degeneration of corticospinal motor axons. They are classified by their mapped genetic loci, SPG1–SPG78. Recently, lysosomal dysfunction is one of the pathomechanism for some autosomal-recessive HSPs. SPG11 is caused by loss-of-function mutations in the SPG11 gene. Its gene product is called spatacsin, which is needed for the recycling of lysosomes from autolysosomes. SPG15 is caused by loss-of-function mutation in the ZFYVE26 gene. The ZFYVE26 gene encodes spastizin. Mutations in spastizin impair autophagosome maturation and lead to an accumulation of immature autophagosomes. SPG48/KIAA0415 encodes AP5Z1, known to be a spatacsin and spastizin interactor. Its mutations lead to loss of protein or mutated forms of protein with defective autophagy. The TECPR2 is a human ATG8-binding protein and positive regulator of autophagy, which plays a key role in major adult and pediatric neurodegenerative diseases. Mutations in the lysosomal trafficking regulator (LYST) gene have been reported to cause hereditary spastic paraplegia. The LYST protein is involved in control of the exocytosis of secretory lysosomes. Recently, Drosophila with a gene mutation of an LYST homolog was revealed to exhibit impaired autophagy.
Part of the book: Lysosomes
Spinal cord disorders are induced by diseases of various categories: infectious, inflammatory, degenerative, genetic, traumatic, and so on. These diseases involve spastic paraplegia or tetraplegia, abnormal sensation, bladder and anal dysfunction, etc. This chapter describes the medical etiologies and treatments for spastic paraplegias. I will mention diagnostic and therapeutic aspects of spastic paraplegias due to non-traumatic spinal cord disorders. I will describe my cases who suffered from amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), HTLV-1 associated myelopathy (HAM), and multiple sclerosis (MS). I also investigate the recent therapeutic strategies for spastic paraplegias. Spastic paraplegia is an intractable condition accompanied by many spinal cord disorders. Some therapeutic methods (intrathecal baclofen and botulinum toxin injection) have symptomatic effects. Rehabilitation and some devices are also effective for spasticity.
Part of the book: Essentials of Spinal Cord Injury Medicine