Sporadic ALS

Excitotoxicity (see Chs 15 and 32) has been suggested to be a mechanism by which motor neurons are damaged in ALS [25,48,49]. About 60-70% of sporadic ALS patients have a 30-95% reduction in the levels of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2), also termed GLT-1, in motor cortex and spinal cord [25, 48, 49]. Reduction in level of activity of this major glutamate transporter leads to increased extracellular concentrations of glutamate at synapses and evidence of excitotoxicity exists in some patients with ALS. 

Kawahara Y., Sun H., Ito K., Hideyama T., Aoki M., Sobue G., Tsuji S., and Kwak S. (2006). Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA. Neurosci. Res. 54 11-14. 

Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE (2005) Prevalence and patterns of cognidve impairment in sporadic ALS. Neurology August 23 65(4) 586—590. 

In ALS, 8-OHdG modified DNA is detected in spinal cord tissues (Calingasan et al., 2005) and CSF (Ihara et al., 2005) from sporadic ALS (SALS) and FALS patients, while levels of nuclear 8-OHdG are increased in motor cortex of SALS patients, but not FALS patients (Shibata et al., 2000). 

However, other authors have found a glutamate deficiency in sporadic ALS brain which is absent in ALS of Guam (Plaitakis et al., 1988 Plaitakis, 1990 Perry et al., 1991). 

This disease shows neuropathological findings of PD and AD loss of neurons and appearance of LB and NFT in cortical and subcortical structures. In the spinal cord of ALS and PD patients of Guam, NFT can be observed. Distribution and number are similar in both diseases. In immunohis-tochemistry, a reactivity against anti-r-protein antibodies has been seen, a result that could not be confirmed by examination of the cytoplasm of sporadic ALS and controls (Kato et al., 1992). 

LH, Veldink JH (2012) Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS. PLoS One 7 e35333 Wikvall K (2001) Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form. Int J Mol Med 7 201-209 2576. 

Sporadic ALS and putative putative retrovi rogen ic-dysmetaboi ic mechanism involving "neuronal-nurturing cells " an X-Y-Z hypothesis regarding this devastating and still-enigmatic disease... 

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