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Amyotrophic Lateral Sclerosis

  1. Orla Hardiman

Published Online: 15 FEB 2010

DOI: 10.1002/9780470015902.a0000014.pub2

eLS

eLS

How to Cite

Hardiman, O. 2010. Amyotrophic Lateral Sclerosis. eLS. .

Author Information

  1. Beaumont Hospital & Trinity College, Department of Neurology, Dublin, Ireland

Publication History

  1. Published Online: 15 FEB 2010
Table 1. Inclusions found in the neurons of patients with amyotrophic lateral sclerosis
Type of inclusionLocationStainingSignificance
Spheroidα Motor neuronSilverNeurofilament
ConglomeratePyramidal Betz cellSilverNeurofilament plus
Bunina bodyα Motor neuronHaematoxylin and eosinUnclear
Eosinophilicα Motor neuronHaematoxylin and eosinNeurofilament plus
SkeinSubcortical neuronAntiubiquitin antibodyUbiquitin positive
Table 2. Known causative genes/loci in familial ALS
NameGeneLocusProtein
  1. Note: VAMP, vesicle-associated membrane protein.

ALS1SOD121q22.1Cu/Zn superoxide dismutase
ALS2ALS22q33-35Alsin
ALS3 18q21 
ALS4SETX9q34Senataxin
ALS5 15q15-q22 
ALS6FUS16q15-q22FUS
ALS7 20ptel 
ALS8VAPB20q13.33VAMP-associated protein
ALS9ANG14q11Angiogenin
ALS10TARDBP1q36TAR DNA-binding-protein-43
ALS-FTD 9q21-22 
ALS-FTD 9p13.2-21,3 
Table 3. Known susceptibility genes for sporadic ALS
GeneFunctional significance
Oxidative stress 
SOD1Cytoplasmic antioxidant soluble form may become neurotoxic
HFE (human hemochromatosis protein)Regulator of iron metabolism
  
Cytoskeleton, microtubule, axonal transport
MAPT (microtubule-associated protein tau)Microtubule protein disruption, involved in other neurodegenerative diseases
NEFH (neurofilament, heavy polypeptide)Neurofilament protein, mutations alter axonal transport
PRPH (peripherin)Intermediate filament, transgenic mice develop motor neuron degeneration
DCT1 (divalent cation transporter 1)Disruption in dynein/dynactin complex alters axonal transport, produces phenotype in mice
  
Metabolism 
PON 1-3 (paroxonase 1-3)Paroxonases are important detoxifying enzymes. Association in five different populations, but different haplotypes implicated in different ancestral populations
ProgranulinGene of major effect in FTD. Coding variations associated with ALS in some populations, similar in function to angiogenin
  
DNA/RNA repair 
ANG (angiogenin, ribonuclease, RNase A family, 5)RNA ribonuclease and hypoxia responsive agent; overlap in function with vascular endothelial growth factor (VEGF) and progranulin
APEXDNA repair enzyme
SMN1 (survival of motor neuron-1), SMN2Affects RNA splicing, gene of major effect in spinal muscular atrophy
TDP-43RNA regulator
  
Unknown 
9p13.2-21,3Also links to familial ALS-FTD
  
Excitotoxicity 
UNC13AAssociated with control of glutamate release