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**5** 

*Italy* 

**Advantages and Pitfalls in** 

*"Maggiore della Carità" Hospital, Novara* 

**Experimental Models Of ALS** 

Marina Boido1, Elisa Buschini1, Antonio Piras1, Giada Spigolon1, Valeria Valsecchi1, Letizia Mazzini2 and Alessandro Vercelli1

*2ALS Centre, Department of Neurology, Eastern Piedmont University,* 

*1Neuroscience Institute of the Cavalieri Ottolenghi Foundation, University of Turin,* 

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that targets upper and lower motoneurons (MN) and leads to death in 2-5 years. 5–10% ALS cases are familial (fALS) with a Mendelian pattern of inheritance. The remaining 90% ALS cases are classified as having sporadic disease (sALS). Only in about 30% of fALS mutations in specific genes have been identified, whereas for the others the etiology is unknown. The

An effective therapy is still lacking, even though many clinical trials have been already conducted. In order to perform preclinical studies to study the etiology and the molecular mechanisms, to design and to test new therapeutic targets and molecules, several *in vitro* and *in vivo* experimental models have been identified, to reproduce the hallmarks of the disease. Such models include transgenic or spontaneously mutated animals as well as *in vitro* preparations, i.e. MN/spinal cord organotypic cultures. Unfortunately, all these models fail to reproduce the complexity of the human disease, even though they represent a

To date, at least 13 genes and loci of major effect in fALS have been identified. The most frequent mutations found in fALS consist in mutations in the gene encoding copper/zinc superoxide dismutase 1 (Cu/Zn SOD1), a ubiquitously expressed enzyme that plays a key role in oxygen free radical scavenging. SOD1 catalyzes the dismutation of superoxide (O2-) to hydrogen peroxide (Scozzafava & Viezzoli, 1993; Tainer et al., 1982). On average, SOD1 mutations are responsible for about 20% of fALS cases (Deng et al., 1993; Rosen et al., 1993) and 5% of apparently sALS (Andersen et al., 2007). Over 70 different mutations at more than 60 residues throughout SOD1 (153 amino acids) have been linked to fALS (Andersen, 2000). The vast majority of mutations are amino acid substitutions, but a few cause C-terminal truncations of the protein. A spontaneous mutation in SOD1 has also been found in a canine

clinical phenotype of fALS is usually indistinguishable from sALS.

very useful tool to investigate several features of the disease.

degenerative myelopathy which resembles ALS (Awano et al., 2009).

**1. Introduction** 

**2. Genetic animal models** 

