**1. Introduction**

The chapter by Aggarwal describes studies in at risk presymtomatic individuals carrying mutant SOD. The research uses MUNE to determine motor neurons status and the thera‐ peutic benefits of riluzole. The methods described in this chapter could provide and early diagnosis in patients carrying mutations linked to ALS allowing presymtomatic treatments. Bocci and collaborators found by Macro-EMG, that there is a possible compensatory over‐ branching in ALS motor neurons, which provides a possible explanation for the adult onset

Abe and collaborators provided a review of the last advances of eye-gaze systems, which allows ALS patient to communicate after almost other voluntary mobility is lost. The tech‐ nology reported here is relatively inexpensive and for those patients unable to communicate

**Alvaro G. Estévez, Ph.D.**

University of Central Florida,

College of Medicine,

USA

Burnett School of Biomedical Sciences,

by other means could represent a significant improvement on quality of life.

of the disease.

VIII Preface

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder character‐ ized by death of pyramidal neurons in the motor cortex (upper motor neurons) and motor neurons in the brain stem and central spinal cord (lower motor neurons). This results in muscle weakness, progressive motor disability, and finally death by respiratory failure or an associated infection (Shook and Pioro, 2009). There are two types of ALS familiar (fALS) and sporadic ALS (sALS). They are both clinically undistiguishale one from the other; fALS accounts for 10% of all cases being the rest of the cases sALS (Pasinelli and Brown, 2006). In the last few years, there had been an explosion of genetic studies associating ALS with several genetic mutations in genes codifying for different proteins: Cu/Zn superoxide dismutase, (SOD1), transactive response binding protein 43 (TARDBP), fused in sarcoma (FUS), and valosin containing protein (VCP). Most recently, a genetic defect was identi‐ fied with an expansion of the noncoding GGGGCC hexanucleotide repeat in the chromo‐ some 9, open reading frame 72 (C9ORF72), associated with ALS with and without frontotemporal dementia (Boeve et al., 2012).

Despite of all these discoveries the etiology of ALS remains elusive. A number of potential pathogenic mechanisms have been associated with ALS including excitotoxicity, mitochon‐ drial dysfunction, apoptosis, glial activation, RNA-processing, growth factor abnormalities, etc. These potential pathogenic processes are reviewed in this chapter.
