Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012:35:25-47.
doi: 10.1146/annurev-neuro-062111-150400. Epub 2012 Apr 20.

Cellular pathways of hereditary spastic paraplegia

Craig Blackstone  1
Affiliations
Review

Cellular pathways of hereditary spastic paraplegia

Craig Blackstone. Annu Rev Neurosci. 2012.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic diagram of the corticospinal tract emphasizing its descent through the CNS. Although most fibers decussate in the caudal medulla, a minority of fibers descend uncrossed as the ventral corticospinal tract (not shown).
Figure 2
Figure 2
Common pathogenic themes in the HSPs. This schematic representation of a corticospinal motor neuron emphasizes where HSP gene products as listed in Table 1 are proposed to function. L1CAM is an integral membrane protein localized to the plasma membrane. CYP7B1 and NTE distributions are not shown, pending more detailed studies of their sites of action.
Figure 3
Figure 3
Spastin, atlastin, REEP, and reticulon proteins interact and shape the endoplasmic reticulum (ER) network. (Left) Schematic diagram of a neuron showing the distribution of different ER domains. Below this schematic is an enlargement of a three-way tubular ER junction. REEP and reticulon proteins form large oligomers to shape the tubular ER. Atlastin proteins are enriched in puncta along the tubules, including at three-way junctions. (Right) Proposed membrane topologies for protein families involved in generating the tubular ER network. GTP, atlastin GTPase domain; MTB, microtubule-binding domain.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

LITERATURE CITED

    1. Abou Jamra R, Philippe O, Raas-Rothschild A, Eck SH, Graf E, et al. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet. 2011;88(6):788–95. - PMC - PubMed
    1. Alazami AM, Adly N, Al Dhalaan H, Alkuraya FS. A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18) Neurogenetics. 2011;12(4):333–36. - PMC - PubMed
    1. Arnold DB. Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons. Sci Signal. 2009;2(83):pe49. - PMC - PubMed
    1. Bakowska JC, Jupille H, Fatheddin P, Puertollano R, Blackstone C. Troyer syndrome protein spartin is mono-ubiquitinated and functions in EGF receptor trafficking. Mol Biol Cell. 2007;18(5):1683–92. - PMC - PubMed
    1. Bakowska JC, Wang H, Xin B, Sumner CJ, Blackstone C. Lack of spartin protein in Troyer syndrome: a loss-of-function disease mechanism? Arch Neurol. 2008;65(4):520–24. - PMC - PubMed

RELATED RESOURCES

    1. Neuromuscul. Dis. Cent. Web page. Familial spinal cord syndromes. http://neuromuscular.wustl.edu/spinal/fsp.html. A comprehensive, frequently updated resource for information on all types of HSPs and related disorders.
    1. Reid E, Rugarli EI. Hereditary spastic paraplegias. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, et al., editors. The Online Metabolic and Molecular Bases of Inherited Diseases. Ch 228.1. New York: McGraw Hill; 2010. http://dx.doi.org/10.1036/ommbid.266. - DOI

    1. Spastic Paraplegia Found. Web page. http://www.sp-foundation.org. Valuable information on research efforts focusing on the HSPs.

Publication types

MeSH terms

Substances