**1. Introduction**

124 Amyotrophic Lateral Sclerosis

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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 clinical phenotype of fALS is usually indistinguishable from sALS.

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 very useful tool to investigate several features of the disease.
