Molecular biology of amyotrophic lateral sclerosis: insights from genetics (original) (raw)

• Mulder, D. W. Clinical limits of amyotrophic lateral sclerosis. Adv. Neurol. 36, 15–22 (1982).
  CAS PubMed Google Scholar
• McGuire, V., Longstreth, W. T. Jr, Koepsell, T. D. & van Belle, G. Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology 47, 571–573 (1996).
  CAS PubMed Google Scholar
• Mitsumoto, H., Chad, D. A. & Pioro, E. P. Amyotrophic Lateral Sclerosis (Oxford Univ. Press, New York, 1998).
  Google Scholar
• Kurtzke, J. K. L. in Clinical Neurology (ed. Joynt, R.) (Lippincott, Philadelphia, 1989).
  Google Scholar
• Kurtzke, J. F. Risk factors in amyotrophic lateral sclerosis. Adv. Neurol. 56, 245–270 (1991).
  CAS PubMed Google Scholar
• Ince, P. G. in Amyotrophic Lateral Sclerosis (eds Brown, R. H. Jr, Meininger, V. & Swash, M.) 83–112 (Martin Dunitz, London, 2000).
  Google Scholar
• Cleveland, D. W. & Rothstein, J. D. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nature Rev. Neurosci. 2, 806–819 (2001).
  CAS Google Scholar
• Rowland, L. P. in Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases (ed. Rowland, L. P.) 3–23 (Raven, 1992).
  Google Scholar
• MacGowan, D. J., Scelsa, S. N. & Waldron, M. An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy. Neurology 57, 1094–1097 (2001).
  CAS PubMed Google Scholar
• Steele, A. J. et al. Detection of serum reverse transcriptase activity in patients with ALS and unaffected blood relatives. Neurology 64, 454–458 (2005).
  CAS PubMed Google Scholar
• Rosen, D. R. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62 (1993). Describes the hallmark discovery that mutations in SOD1 cause ALS in a subset of familial cases.
  CAS PubMed Google Scholar
• Yang, Y. et al. The gene encoding alsin, a protein with three guaninenucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nature Genet. 29, 160–165 (2001).
  CAS PubMed Google Scholar
• Hadano, S. et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nature Genet. 29, 166–173 (2001).
  CAS PubMed Google Scholar
• Chance, P. F. Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. Am. J. Hum. Genet. 62, 633–640 (1998).
  CAS PubMed PubMed Central Google Scholar
• Chen, Y. Z. et al. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am. J. Hum. Genet. 74, 1128–1135 (2004).
  CAS PubMed PubMed Central Google Scholar
• Nishimura, A. L. et al. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet. 75, 822–831 (2004).
  CAS PubMed PubMed Central Google Scholar
• Puls, I. et al. Mutant dynactin in motor neuron disease. Nature Genet. 33, 455–456 (2003). References 12–17 describe ALS-causing gene mutations.
  CAS PubMed Google Scholar
• Ruddy, D. M. et al. Two families with familial amyotrophic lateral sclerosis are linked to a novel locus on chromosome 16q. Am. J. Hum. Genet. 73, 390–396 (2003).
  CAS PubMed PubMed Central Google Scholar
• Hentati, A. et al. Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers. Neurogenetics 2, 55–60 (1998).
  CAS PubMed Google Scholar
• Sapp, P. et al. Identification of three novel mutations in the gene for Cu/Zn superoxide dismutase in patients with familial amyotrophic lateral sclerosis. Neuromuscul. Disord. 5, 353–357 (1995).
  CAS PubMed Google Scholar
• Abalkhail, H., Mitchell, J., Habgood, J., Orrell, R. & de Belleroche, J. A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1–16q12.2. Am. J. Hum. Genet. 73, 383–389 (2003).
  CAS PubMed PubMed Central Google Scholar
• Hong, S. et al. X-linked dominant locus for late-onset familial amyotrophic lateral sclerosis. Soc. Neurosci. Abstr. 24, 478 (1998).
  Google Scholar
• Hand, C. K. et al. A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q. Am. J. Hum. Genet. 70, 251–256 (2002).
  CAS PubMed Google Scholar
• Morita, M. et al. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology 66, 839–844 (2006).
  CAS PubMed Google Scholar
• Hosler, B. A. et al. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21–q22. JAMA 284, 1664–1669 (2000).
  CAS PubMed Google Scholar
• Andersen, P. M. et al. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 4, 62–73 (2003).
  CAS PubMed Google Scholar
• Andersen, P. M. et al. Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia. Brain 120, 1723–1737 (1997).
  PubMed Google Scholar
• Radunovic, A. et al. Copper and zinc levels in familial amyotrophic lateral sclerosis patients with Cu/Zn gene mutations. Ann. Neurol. 42, 130–131 (1997).
  CAS PubMed Google Scholar
• Yamanaka, K. & Cleveland, D. W. Determinants of rapid disease progression in ALS. Neurology 65, 1859–1860 (2005).
  PubMed Google Scholar
• Cudkowicz, M. E., McKenna-Yasek, D., Chen, C., Hedley-Whyte, E. T. & Brown, R. H. Jr. Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene [see comments]. Ann. Neurol. 43, 703–710 (1998).
  CAS PubMed Google Scholar
• Andersen, P. M. et al. Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation. A clinical and genealogical study of 36 patients. Brain 119, 1153–1172 (1996).
  PubMed Google Scholar
• Soares, M. L. et al. Haplotypes and DNA sequence variation within and surrounding the transthyretin gene: genotype-phenotype correlations in familial amyloid polyneuropathy (V30M) in Portugal and Sweden. Eur. J. Hum. Genet. 12, 225–237 (2004).
  CAS PubMed Google Scholar
• Topp, J. D., Gray, N. W., Gerard, R. D. & Horazdovsky, B. F. Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. J. Biol. Chem. 23, 24612–24623 (2004).
  Google Scholar
• Otomo, A. et al. ALS2, a novel guanine nucleotide exchange factor for the small GTPase Rab5, is implicated in endosomal dynamics. Hum. Mol. Genet. 12, 1671–1687 (2003).
  CAS PubMed Google Scholar
• Kanekura, K. et al. Alsin, the product of ALS2 gene, suppresses SOD1 mutant neurotoxicity through RhoGEF domain by interacting with SOD1 mutants. J. Biol. Chem. 279, 19247–19256 (2004).
  CAS PubMed Google Scholar
• Panzeri, C. et al. The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain 129, 1710–1719 (2006).
  PubMed Google Scholar
• Yamanaka, K. et al. Unstable mutants in the peripheral endosomal membrane component ALS2 cause early-onset motor neuron disease. Proc. Natl Acad. Sci. USA 100, 16041–16046 (2003).
  CAS PubMed Google Scholar
• Cai, H. et al. Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress. J. Neurosci. 25, 7567–7574 (2005).
  CAS PubMed PubMed Central Google Scholar
• Hadano, S. et al. Mice deficient in the Rab5 guanine nucleotide exchange factor ALS2/alsin exhibit age-dependent neurological deficits and altered endosome trafficking. Hum. Mol. Genet. 15, 233–250 (2006).
  CAS PubMed Google Scholar
• Chen, Y. Z. et al. Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in which recessive mutations cause ataxia and dominant mutations cause motor neuron disease. Neurobiol. Dis. 23, 97–108 (2006).
  CAS PubMed Google Scholar
• Skibinski, G. et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nature Genet. 37, 806–808 (2005).
  CAS PubMed Google Scholar
• Comi, G. P. et al. Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann. Neurol. 43, 110–116 (1998).
  CAS PubMed Google Scholar
• Borthwick, G. M. et al. Motor neuron disease in a patient with a mitochondrial tRNAIle mutation. Ann. Neurol. 59, 570–574 (2006).
  CAS PubMed Google Scholar
• Lambrechts, D. et al. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nature Genet. 34, 383–394 (2003).
  CAS PubMed Google Scholar
• Van Vught, P. W. et al. Lack of association between VEGF polymorphisms and ALS in a Dutch population. Neurology 65, 1643–1645 (2005).
  CAS PubMed Google Scholar
• Greenway, M. J. et al. A novel candidate region for ALS on chromosome 14q11.2. Neurology 63, 1936–1938 (2004).
  CAS PubMed Google Scholar
• Al-Chalabi, A. et al. Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum. Mol. Genet. 8, 157–164 (1999).
  CAS PubMed Google Scholar
• Figlewicz, D. A. et al. Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum. Mol. Genet. 3, 1757–1761 (1994).
  CAS PubMed Google Scholar
• Tomkins, J. et al. Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9, 3967–3970 (1998).
  CAS PubMed Google Scholar
• Corcia, P. et al. Abnormal SMN1 gene copy number is a susceptibility factor for amyotrophic lateral sclerosis. Ann. Neurol. 51, 243–246 (2002).
  CAS PubMed Google Scholar
• Veldink, J. H. et al. Homozygous deletion of the survival motor neuron 2 gene is a prognostic factor in sporadic ALS. Neurology 56, 749–752 (2001).
  CAS PubMed Google Scholar
• Reaume, A. et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nature Genet. 13, 43–47 (1996).
  CAS PubMed Google Scholar
• Gurney, M. Mutant mice, Cu, Zn superoxide dismutase, and motor neuron degeneration. Science 266, 1586 (1994). The first description of the transgenic mouse model of ALS.
  Google Scholar
• Cleveland, D. W., Laing, N., Hurse, P. V. & Brown, R. H. Jr. Toxic mutants in Charcot's sclerosis [letter; comment]. Nature 378, 342–343 (1995).
  CAS PubMed Google Scholar
• Beckman, J. S., Carson, M., Smith, C. D. & Kuppenol, W. H. ALS, SOD, and peroxynitrite. Nature 364, 584 (1993).
  CAS PubMed Google Scholar
• Wiedau-Pazos, M. et al. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science 271, 515–518 (1996).
  CAS PubMed Google Scholar
• Estevez, A. G. et al. Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286, 2498–2500 (1999).
  CAS PubMed Google Scholar
• Andrus, P. K., Fleck, T. J., Gurney, M. E. & Hall, E. D. Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 71, 2041–2048 (1998).
  CAS PubMed Google Scholar
• Hall, E., Andrus, P., Oostveen, J., Fleck, T. & Gurney, M. Relationship of oxygen radical-induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J. Neurosci. Res. 53, 66–77 (1998).
  CAS PubMed Google Scholar
• Bruijn, L. et al. Elevated free nitrotyrosine levels but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-liked superoxide dismutase 1 mutant. Proc. Natl Acad. Sci. USA 94, 7606–7611 (1997).
  CAS PubMed Google Scholar
• Bruijn, L. I. et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 281, 1851–1854 (1998).
  CAS PubMed Google Scholar
• Jaarsma, D. et al. Human Cu/Zn superoxide dismutase (SOD1) overexpression in mice causes mitochondrial vacuolization, axonal degeneration, and premature motoneuron death and accelerates motoneuron disease in mice expressing a familial amyotrophic lateral sclerosis mutant SOD1. Neurobiol. Dis. 7, 623–643 (2000).
  CAS PubMed Google Scholar
• Deng, H. X. et al. Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. Proc. Natl Acad. Sci. USA 103, 7142–7147 (2006).
  CAS PubMed Google Scholar
• Wong, P. C. et al. Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. Proc. Natl Acad. Sci. USA 97, 2886–2891 (2000).
  CAS PubMed Google Scholar
• Wang, J. et al. Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature. Hum. Mol. Genet. 12, 2753–2764 (2003).
  CAS PubMed Google Scholar
• Ripps, M. E., Huntley, G. W., Hof, P. R., Morrison, J. H. & Gordon, J. W. Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. Proc. Natl Acad. Sci. USA 92, 689–693 (1995).
  CAS PubMed Google Scholar
• Bush, A. I. Is ALS caused by an altered oxidative activity of mutant superoxide dismutase? Nature Neurosci. 5, 919; author reply 919–920 (2002).
  CAS PubMed Google Scholar
• Jonsson, P. A. et al. Disulphide-reduced superoxide dismutase-1 in CNS of transgenic amyotrophic lateral sclerosis models. Brain 129, 451–464 (2006).
  PubMed Google Scholar
• Johnston, J. A., Dalton, M. J., Gurney, M. E. & Kopito, R. R. Formation of high molecular weight complexes of mutant Cu,Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc. Natl Acad. Sci. USA 97, 12571–12576 (2000).
  CAS Google Scholar
• Wang, J., Xu, G. & Borchelt, D. R. High molecular weight complexes of mutant superoxide dismutase 1: age-dependent and tissue-specific accumulation. Neurobiol. Dis. 9, 139–148 (2002).
  CAS PubMed Google Scholar
• Ray, S. S. et al. An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis. Biochemistry 43, 4899–4905 (2004).
  CAS PubMed Google Scholar
• Matsumoto, G., Kim, S. & Morimoto, R. I. Huntingtin and mutant SOD1 form aggregate structures with distinct molecular properties in human cells. J. Biol. Chem. 281, 4477–4485 (2006).
  CAS PubMed Google Scholar
• Sato, T. et al. Rapid disease progression correlates with instability of mutant SOD1 in familial ALS. Neurology 65, 1954–1957 (2005).
  CAS PubMed Google Scholar
• Lindberg, M. J., Bystrom, R., Boknas, N., Andersen, P. M. & Oliveberg, M. Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants. Proc. Natl Acad. Sci. USA 102, 9754–9759 (2005).
  CAS PubMed Google Scholar
• Shinder, G. A., Lacourse, M. -C., Minotti, S. & Durham, H. D. Mutant cu/zn superoxide dismutase proteins have altered solubility and interact with heat shock/stress proteins in models of amyotrophic lateral sclerosis. J. Biol. Chem. 276, 12791–12796 (2001).
  CAS PubMed Google Scholar
• Pasinelli, P. et al. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43, 19–30 (2004).
  CAS PubMed Google Scholar
• Guegan, C. & Przedborski, S. Programmed cell death in amyotrophic lateral sclerosis. J. Clin. Invest. 111, 153–161 (2003).
  CAS PubMed PubMed Central Google Scholar
• Durham, H., Roy, J., Dong, L. & Figlewicz, D. Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS. J. Neuropath. Exp. Neurol. 56, 523–530 (1997).
  CAS PubMed Google Scholar
• Pasinelli, P., Borchelt, D. R., Houseweart, M. K., Cleveland, D. W. & Brown, R. H. Jr. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proc. Natl Acad. Sci. USA 95, 15763–15768 (1998).
  CAS PubMed Google Scholar
• Pasinelli, P., Houseweart, M. K., Brown, R. H. Jr & Cleveland, D. W. Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis. Proc. Natl Acad. Sci. USA 97, 13901–13906 (2000).
  CAS PubMed Google Scholar
• Vukosavic, S. et al. Delaying caspase activation by Bcl-2: a clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurosci. 20, 9119–9125 (2000).
  CAS PubMed Google Scholar
• Li, M. et al. Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 288, 335–339 (2000).
  CAS PubMed Google Scholar
• Vukosavic, S., Dubois-Dauphin, M., Romero, N. & Przedborski, S. Bax and Bcl-2 intercation in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 73, 2460–2468 (1999).
  CAS PubMed Google Scholar
• Bacman, S. R., Bradley, W. G. & Moraes, C. T. Mitochondrial involvement in amyotrophic lateral sclerosis: trigger or target? Mol. Neurobiol. 33, 113–131 (2006).
  CAS PubMed Google Scholar
• Boston-Howes, W. et al. Caspase-3 cleaves and inactivates the glutamate transporter EAAT2. J. Biol. Chem. 281, 14076–14084 (2006).
  CAS PubMed Google Scholar
• Guegan, C., Vila, M., Rosoklija, G., Hays, A. P. & Przedborski, S. Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis. J. Neurosci. 21, 6569–6576 (2001).
  CAS PubMed Google Scholar
• Rabizadeh, S. et al. Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells. Proc. Natl Acad. Sci. USA 92, 3024–3028 (1995).
  CAS PubMed Google Scholar
• Alexianu, M. E., Kozovska, M. & Appel, S. H. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 57, 1282–1289 (2001).
  CAS PubMed Google Scholar
• Elliott, J. L. Cytokine upregulation in a murine model of familial amyotrophic lateral sclerosis. Brain Res. Mol. Brain Res. 95, 172–178 (2001).
  CAS PubMed Google Scholar
• Almer, G. et al. Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann. Neurol. 49, 176–185 (2001).
  CAS PubMed Google Scholar
• Hensley, K. et al. Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation. J. Neuroinflammation 3, 2 (2006).
  PubMed PubMed Central Google Scholar
• Raoul, C. et al. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron 35, 1067–1083 (2002).
  CAS PubMed Google Scholar
• Raoul, C. et al. Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL. Proc. Natl Acad. Sci. USA 103, 6007–6012 (2006).
  CAS PubMed Google Scholar
• Kikuchi, H. et al. Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model. Proc. Natl Acad. Sci. USA 103, 6025–6030 (2006).
  CAS PubMed Google Scholar
• Urushitani, M. et al. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nature Neurosci. 9, 108–118 (2006).
  CAS PubMed Google Scholar
• Atsumi, T. The ultrastructure of intramuscular nerves in amyotrophic lateral sclerosis. Acta Neuropath. 55, 193–198 (1981).
  CAS PubMed Google Scholar
• Afifi, A., Aleu, F., Goodgold, J. & MacKay, B. Ultrastructure of atrophic muscle in amyotrophic lateral sclerosis. Neurology 16, 475–481 (1966).
  CAS PubMed Google Scholar
• Wiedemann, F. R. et al. Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J. Neurol. Sci. 156, 65–72 (1998).
  CAS PubMed Google Scholar
• Siklos, L. et al. Ultrastructural evidence for altered calcium in motor nerve terminals in amyotrophic lateral sclerosis. Ann. Neurol. 39, 203–216 (1996).
  CAS PubMed Google Scholar
• Higgins, C. M., Jung, C. & Xu, Z. ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci. 4, 16 (2003).
  PubMed PubMed Central Google Scholar
• Kong, J. & Xu, Z. Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J. Neurosci. 18, 3241–3250 (1998).
  CAS PubMed Google Scholar
• Bendotti, C. et al. Early vacuolization and mitochondrial damage in motor neurons of FALS mice are not associated with apoptosis or with changes in cytochrome oxidase histochemical reactivity. J. Neurol. Sci. 191, 25–33 (2001).
  CAS PubMed Google Scholar
• Sasaki, S., Warita, H., Murakami, T., Abe, K. & Iwata, M. Ultrastructural study of mitochondria in the spinal cord of transgenic mice with a G93A mutant SOD1 gene. Acta Neuropathol. (Berl.) 107, 461–474 (2004).
  Google Scholar
• Rizzardini, M. et al. Neurodegeneration induced by complex I inhibition in a cellular model of familial amyotrophic lateral sclerosis. Brain Res. Bull. 69, 465–474 (2006).
  CAS PubMed Google Scholar
• Jung, C., Higgins, C. M. & Xu, Z. Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. J. Neurochem. 83, 535–545 (2002).
  CAS PubMed Google Scholar
• Damiano, M. et al. Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J. Neurochem. 96, 1349–1361 (2006).
  CAS PubMed Google Scholar
• Menzies, F. M. et al. Mitochondrial dysfunction in a cell culture model of familial amyotrophic lateral sclerosis. Brain 125, 1522–1533 (2002).
  PubMed Google Scholar
• Klivenyi, P. et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Med. 5, 347–350 (1999).
  CAS PubMed Google Scholar
• Zhu, S. et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417, 74–78 (2002).
  CAS PubMed Google Scholar
• Higgins, C. M., Jung, C., Ding, H. & Xu, Z. Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS. J. Neurosci. 22, RC215 (2002).
  PubMed Google Scholar
• Mattiazzi, M. et al. Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J. Biol. Chem. 277, 29626–29633 (2002).
  CAS PubMed Google Scholar
• Liu, J. et al. Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43, 5–17 (2004).
  CAS PubMed Google Scholar
• Okado-Matsumoto, A. & Fridovich, I. Amyotrophic lateral sclerosis: a proposed mechanism. Proc. Natl Acad. Sci. USA 99, 9010–9014 (2002).
  CAS PubMed Google Scholar
• Takeuchi, H. K., Ishigaki, Y., Doyu, S. M. & Sobue, G. Mitochondrial localization of mutant superoxide dismutase 1 triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis. J. Biol. Chem. 277, 50966–50972 (2002).
  CAS PubMed Google Scholar
• Bergemalm, D. et al. Overloading of stable and exclusion of unstable human superoxide dismutase-1 variants in mitochondria of murine amyotrophic lateral sclerosis models. J. Neurosci. 26, 4147–4154 (2006).
  CAS PubMed Google Scholar
• Sasaki, S. & Iwata, M. Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotrophic lateral sclerosis. Neurology 47, 535–540 (1996).
  CAS PubMed Google Scholar
• Sasaki, S., Warita, H., Abe, K. & Iwata, M. Impairment of axonal transport in the axon hillock and the initial segment of anterior horn neurons in transgenic mice with a G93A mutant SOD1 gene. Acta Neuropathol. (Berl.) 100, 48–56 (2005).
  Google Scholar
• Zhang, B., Tu, P., Abtahian, F., Trojanowski, J. Q. & Lee, V. M. Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J. Cell Biol. 139, 1307–1315 (1997).
  CAS PubMed PubMed Central Google Scholar
• Borchelt, D. R. et al. Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice. Neurobiol. Dis. 5, 27–35 (1998).
  CAS PubMed Google Scholar
• Williamson, T. & Cleveland, D. Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutant to motor neurons. Nature Neurosci. 1, 50–56 (1999).
  Google Scholar
• Murakami, T. et al. Impaired retrograde axonal transport of adenovirus-mediated E. coli LacZ gene in the mice carrying mutant SOD1 gene. Neurosci. Lett. 308, 149–152 (2001).
  CAS PubMed Google Scholar
• Rao, M. V. & Nixon, R. A. Defective neurofilament transport in mouse models of amyotrophic lateral sclerosis: a review. Neurochem. Res. 28, 1041–1047 (2003).
  CAS PubMed Google Scholar
• Ligon L. A. et al. Mutant superoxide dismutase disrupts cytoplasmic dynein in motor neurons. Neuroreport 16, 533–536 (2005).
  CAS PubMed Google Scholar
• Witherden, A. S. et al. An integrated genetic, radiation hybrid, physical and transcription map of a region of distal mouse chromosome 12, including an imprinted locus and the 'Legs at odd angles' (Loa) mutation. Gene 283, 71–82 (2002).
  CAS PubMed Google Scholar
• Hafezparast, M. et al. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300, 808–812 (2003).
  CAS PubMed Google Scholar
• LaMonte, B. H. et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34, 715–727 (2002).
  CAS PubMed Google Scholar
• Kieran, D. et al. A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J. Cell Biol. 169, 561–567 (2005).
  CAS PubMed PubMed Central Google Scholar
• Teuchert, M. et al. A dynein mutation attenuates motor neuron degeneration in SOD1(G93A) mice. Exp. Neurol. 198, 271–274 (2006).
  CAS PubMed Google Scholar
• Vande Velde, C., Garcia, M. L., Yin, X., Trapp, B. D. & Cleveland, D. W. The neuroprotective factor Wlds does not attenuate mutant SOD1-mediated motor neuron disease. Neuromolecular Med. 5, 193–203 (2004).
  CAS PubMed Google Scholar
• Pigino, G. et al. Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport. J. Neurosci. 23, 4499–4508 (2003).
  CAS PubMed Google Scholar
• Morfini, G., Pigino, G., Beffert, U., Busciglio, J. & Brady, S. T. Fast axonal transport misregulation and Alzheimer's disease. Neuromolecular Med. 2, 89–99 (2002).
  CAS PubMed Google Scholar
• Trushina, E. et al. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell Biol. 24, 8195–8209 (2004).
  CAS PubMed PubMed Central Google Scholar
• Schmitt-John, T. et al. Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nature Genet. 37, 1213–1215 (2005).
  CAS PubMed Google Scholar
• Rothstein, J., Kammen, M., Levey, A., Martin, L. & Kuncl, R. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol. 38, 73–84 (1995).
  CAS PubMed Google Scholar
• Rothstein, J. D. et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann. Neurol. 28, 18–25 (1990).
  CAS PubMed Google Scholar
• Rothstein, J. D., Martin, L. J. & Kuncl, R. W. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis [see comments]. N. Engl. J. Med. 326, 1464–1468 (1992).
  CAS PubMed Google Scholar
• Arriza, J. L. et al. Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci. 14, 5559–5569 (1994).
  CAS Google Scholar
• Arriza, J. L., Eliasof, S., Kavanaugh, M. P. & Amara, S. G. Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl Acad. Sci. USA 94, 4155–4160 (1997).
  CAS PubMed Google Scholar
• Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P. & Amara, S. G. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375, 599–603 (1995).
  CAS PubMed Google Scholar
• Trotti, D., Rolfs, A., Danbolt, N. C., Brown, R. H. Jr & Hediger, M. A. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nature Neurosci 2, 848 (1999).
  CAS PubMed Google Scholar
• Howland, D. S. et al. Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc. Natl Acad. Sci. USA 99, 1604–1609 (2002).
  CAS PubMed Google Scholar
• Lin, C. L. et al. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron 20, 589–602 (1998).
  CAS PubMed Google Scholar
• Aoki, M. et al. Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis. Ann. Neurol. 43, 645–653 (1998).
  CAS PubMed Google Scholar
• Trotti, D. et al. Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity. J. Biol. Chem. 276, 576–582 (2001).
  CAS PubMed Google Scholar
• Alexianu, M. E. et al. The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis. Ann. Neurol. 36, 846–858 (1994).
  CAS PubMed Google Scholar
• Williams, D. N. C. & Ince, P. G. α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis. Ann. Neurol. 42, 200–207 (1997).
  CAS PubMed Google Scholar
• Ince, P. G., Shaw, P. J., Slade, J. Y., Jones, C. & Hudgson, P. Familial amyotrophic lateral sclerosis with a mutation in exon 4 of the Cu/Zn superoxide dismutase gene: pathological and immunocytochemical changes. Acta Neuropathol. (Berl.) 92, 395–403 (1996).
  CAS Google Scholar
• Pramatarova, A., Laganiere, J., Roussel, J., Brisebois, K. & Rouleau, G. A. Neuron specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor neuron impairment. J. Neurosci. 21, 3369–3374 (2001).
  CAS PubMed Google Scholar
• Gong, Y. H., Parsadanian, A. S., Andreeva, A., Snider, W. D. & Elliott, J. L. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J. Neurosci. 20, 660–665 (2000).
  CAS PubMed Google Scholar
• Clement, A. M. et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302, 113–117 (2003). Demonstrates the importance of non-neuronal cells in ALS pathogenesis.
  CAS PubMed Google Scholar
• Boillee, S. et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312, 1389–1392 (2006). Elegantly highlights the importance of microglia for disease progression in transgenic ALS mice.
  CAS PubMed Google Scholar
• Wang, J. et al. Coincident thresholds of mutant protein for paralytic disease and protein aggregation caused by restrictively expressed superoxide dismutase cDNA. Neurobiol. Dis. 20, 943–952 (2005).
  CAS PubMed Google Scholar
• Lefebvre, S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155–165 (1995).
  CAS PubMed Google Scholar
• Mersiyanova, I. V. et al. A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Am. J. Hum. Genet. 67, 37–46 (2000).
  CAS PubMed PubMed Central Google Scholar
• Bomont, P. et al. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nature Genet. 26, 370–374 (2000).
  CAS PubMed Google Scholar
• Kuhlenbaumer, G. Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene. Neurology 58, 1273–1276 (2002).
  CAS PubMed Google Scholar
• Zhao, C. et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bβ. Cell 105, 587–597 (2001).
  CAS PubMed Google Scholar
• Zuchner, S. et al. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Nature Genet. 37, 289–294 (2005).
  PubMed Google Scholar
• Zhao, X. et al. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nature Genet. 29, 326–331 (2001).
  CAS PubMed Google Scholar
• Verhoeven, K. et al. Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am. J. Hum. Genet. 72, 722–727 (2003).
  CAS PubMed PubMed Central Google Scholar
• Patel, H. et al. SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nature Genet. 31, 347–348 (2002).
  CAS PubMed Google Scholar
• Antonellis, A. et al. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am. J. Hum. Genet. 72, 1293–1299 (2003).
  CAS PubMed PubMed Central Google Scholar
• Jordanova, A. et al. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nature Genet. 38, 197–202 (2006).
  CAS PubMed Google Scholar
• Kalaydjieva, L. et al. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. Am. J. Hum. Genet. 67, 47–58 (2000).
  CAS PubMed PubMed Central Google Scholar
• Grohmann, K. et al. Mutations in the gene encoding immunoglobulin mubinding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nature Genet. 29, 75–77 (2001).
  CAS PubMed Google Scholar
• Evgrafov, O. V. et al. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nature Genet. 36, 602–606 (2004).
  CAS PubMed Google Scholar
• Irobi, J., De Jonghe, P. & Timmerman, V. Molecular genetics of distal hereditary motor neuropathies. Hum. Mol. Genet. 13, R195–R202 (2004).
  CAS PubMed Google Scholar
• White, R. J. & Reynolds, I. J. Mitochondrial depolarization in glutamate-stimulated neurons: an early signal specific to excitotoxin exposure. J. Neurosci. 16, 5688–5697 (1996).
  CAS PubMed Google Scholar
• Roa, B. B., Garcia, C. A. & Lupski, J. R. Charcot-Marie-Tooth disease type 1A: molecular mechanisms of gene dosage and point mutation underlying a common inherited peripheral neuropathy. Int. J. Neurol. 25–26, 97–107 (1991).
  PubMed Google Scholar
• Hayasaka, K. et al. De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III). Nature Genet. 5, 266–268 (1993).
  CAS PubMed Google Scholar
• Street, V. A. et al. Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C. Neurology 60, 22–26 (2003).
  CAS PubMed Google Scholar
• Warner, L. E. et al. Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nature Genet. 18, 382–384 (1998).
  CAS PubMed Google Scholar
• Baxter, R. V. et al. Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21. Nature Genet. 30, 21–22 (2002).
  CAS PubMed Google Scholar
• Bolino, A. et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nature Genet. 25, 17–19 (2000).
  CAS PubMed Google Scholar
• Senderek, J. et al. Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15. Hum. Mol. Genet. 12, 349–356 (2003).
  CAS PubMed Google Scholar
• Senderek, J. et al. Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy. Am. J. Hum. Genet. 73, 1106–1119 (2003).
  CAS PubMed PubMed Central Google Scholar
• Boerkoel, C. F. et al. Periaxin mutations cause recessive Dejerine-Sottas neuropathy. Am. J. Hum. Genet. 68, 325–333 (2001).
  CAS PubMed Google Scholar
• Bergoffen, J. et al. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science 262, 2039–2042 (1993).
  CAS PubMed Google Scholar
• Bruijn, L. I. & Cudkowicz, M. Therapeutic targets for amyotrophic lateral sclerosis: current treatments and prospects for more effective therapies. Expert Rev. Neurother. 6, 417–428 (2006).
  CAS PubMed Google Scholar
• Kaspar, B. K., Llado, J., Sherkat, N., Rothstein, J. D. & Gage, F. H. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301, 839–842 (2003). Describes an effective therapy in ALS mice based on the delivery of insulin-like growth factor 1 (IGF1) to motor neurons via a retrogradely transported AAV2–IGF1 gene therapy vector.
  CAS PubMed Google Scholar
• Raoul, C. et al. Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nature Med. 11, 423–428 (2005).
  CAS PubMed Google Scholar
• Ralph, G. S. et al. Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nature Med. 11, 429–433 (2005). References 180 and 181 present compelling evidence that the process of motor neuron cell death in ALS mice can be slowed using inhibitory RNA to silence the offending, mutated SOD1 genes.
  CAS PubMed Google Scholar
• Ralph, G. S., Mazarakis, N. D. & Azzouz, M. Therapeutic gene silencing in neurological disorders, using interfering RNA. J. Mol. Med. 83, 413–419 (2005).
  CAS PubMed Google Scholar
• Maxwell, M. M., Pasinelli, P., Kazantsev, A. G. & Brown, R. H. Jr. RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells. Proc. Natl Acad. Sci. USA 101, 3178–3185 (2004).
  CAS PubMed Google Scholar
• Miller, T. M. et al. Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis. Ann. Neurol. 57, 773–776 (2005).
  CAS PubMed PubMed Central Google Scholar
• Smith, R. A. et al. Antisense oligonucleotide therapy for neurodegenerative disease. J. Clin. Invest. 116, 2290–2296 (2006).
  CAS PubMed PubMed Central Google Scholar
• Wills, A. M. & Brown, R. H. Jr in Amyotrophic Lateral Sclerosis Ch. 14 (eds Brown, R. H. Jr, Swash, M. & Pasinelli, P.) 269–282 (Taylor & Francis, Abingdon, 2006).
  Google Scholar
• Zuchner, S. et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nature Genet. 36, 449–451 (2004).
  PubMed Google Scholar
• Zuchner, S. et al. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Nature Genet. 37, 289–294 (2005).
  PubMed Google Scholar
• Verhoeven, K. et al. Slowed conduction and thin myelination of peripheral nerves associated with mutant rho Guanine-nucleotide exchange factor 10. Am. J. Hum. Genet. 73, 926–932 (2003).
  CAS PubMed PubMed Central Google Scholar
• Bejaoui, K. et al. SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nature Genet. 27, 261–262 (2001).
  CAS PubMed Google Scholar
• Grandchamp, B. et al. Tissue-specific splicing mutation in acute intermittent porphyria. Proc. Natl Acad. Sci. USA 86, 661–664 (1989).
  CAS PubMed Google Scholar
• Goizet, C. et al. A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J. Med. Genet. 41, e29 (2004).
  CAS PubMed PubMed Central Google Scholar
• DeSandre-Giovannoli, A. et al. Homozygous defects in LMNa, encoding lamin A/C nuclear envelope proteins, cause autosomal recessive neuropathy in human (Charcot-Marie Tooth disorder, Type 2) and mouse. Am. J. Hum. Gen. 70, 726–736 (2002).
  CAS Google Scholar
• Howard, H. C. et al. The K–Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum. Nature Genet. 32, 384–392 (2002).
  CAS PubMed Google Scholar
• Indo, Y. et al. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nature Genet. 13, 485–488 (1996).
  CAS PubMed Google Scholar
• Kihara, H., Fluharty, A. L., O'Brien, J. S. & Fish, C. H. Metachromatic leukodystrophy caused by a partial cerebroside sulfatase. Clin. Genet. 21, 253–261 (1982).
  CAS PubMed Google Scholar
• Mihalik, S. J. et al. Identification of PAHX, a Refsum disease gene. Nature Genet. 17, 185–189 (1997).
  CAS PubMed Google Scholar
• Anderson, S. L. et al. Familial dysautonomia is caused by mutations of the IKAP gene. Am. J. Hum. Genet. 68, 753–758 (2001).
  CAS PubMed PubMed Central Google Scholar
• Rust, S. et al. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nature Genet. 22, 352–355 (1999).
  CAS PubMed Google Scholar
• La Spada, A. R., Wilson, E. M., Luban, D. B., Harding, A. E. & Fischbeck, K. H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991).
  CAS PubMed Google Scholar
• Yamada, K. et al. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nature Genet. 35, 318–321 (2003).
  CAS PubMed Google Scholar
• Takeda, K. et al. Fine assignment of β-hexosaminidase A α subunit on 15q23–24 by high resolution in situ hybridization. Tohoku J. Exp. Med. 160, 203–211 (1990).
  CAS PubMed Google Scholar
• Windpassinger, C. et al. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nature Genet. 36, 271–276 (2004).
  CAS PubMed Google Scholar
• Hansen, J. J. et al. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet. 70, 1328–1332 (2002).
  CAS PubMed PubMed Central Google Scholar
• Reid, E. et al. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am. J. Hum. Genet. 71, 1189–1194 (2002).
  CAS PubMed PubMed Central Google Scholar
• Rainier, S., Chai, J. H., Tokarz, D., Nicholls, R. D. & Fink, J. K. NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am. J. Hum. Genet. 73, 967–971 (2003).
  CAS PubMed PubMed Central Google Scholar
• Hazan, J. et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nature Genet. 23, 296–303 (1999).
  CAS PubMed Google Scholar
• O'Neill, B. P., Swanson, J. W., Brown, F. R., Griffin, J. W. & Moser, H. W. Familial spastic paraparesis: an adrenoleukodystrophy phenotype? Neurology 35, 1233–1235 (1985).
  CAS PubMed Google Scholar
• Simpson, M. A. et al. Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia. Am. J. Hum. Genet. 73, 1147–1156 (2003).
  CAS PubMed PubMed Central Google Scholar
• Casari, G. et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93, 973–983 (1998).
  CAS PubMed Google Scholar
• Touraine, R. L. et al. Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain. Am. J. Hum. Genet. 66, 1496–1503 (2000).
  CAS PubMed PubMed Central Google Scholar
• Jouet, M. et al. X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result in mutations in the L1 gene. Nature Genet. 7, 402–407 (1994).
  CAS PubMed Google Scholar
• Saugier-Veber, P. et al. X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic disorders at the proteolipid protein locus. Nature Genet. 6, 257–262 (1994).
  CAS PubMed Google Scholar