Abstract: Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related to mutations in causative genes, while the vast majority of amyotrophic lateral sclerosis cases are considered to be sporadic, resulting from the interaction between genes and environmental factors in predisposed individuals. During the past few years, dozens of drugs have been postulated as promising strategies for the disease after showing some beneficial effects in preclinical cellular and murine models. However, the translation into clinical practice has been largely unsuccessful and the compounds failed when were tested in clinical trials. This might be explained, at least partially, by the enormous complexity of the disease both from clinico-epidemiological and a pathogenic points of view. In this review, we will briefly comment on the complexity of the disease focusing on some recent findings, and we will suggest how amyotrophic lateral sclerosis research might be reoriented to foster the advance in the diagnostic and therapeutic questions.
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