Contents

#### **Preface XI**



Preface

the disease.

the human disease.

The research in amyotrophic lateral sclerosis (ALS) has dramatically increased in the last 20 years, greatly improving our understanding of the pathological mechanisms involved in the disease. The number of hypothesis on the pathogenic causes of ALS and the mechanisms of motor neuron death keeps growing. Twenty years ago there was a general agreement that ALS was a motor neuron disease. All other symptoms were secondary to the primary cause that was the death of upper and lower motor neurons. Today there are several hypotheses suggesting that dysfunction in other cell types, such as astrocytes, is the primary cause of the disease that leads to motor neuron death. Twenty years ago there were not animal mod‐ els for ALS, now there are multiple rodent and non-mammalian models of the disease.

The more accepted hypotheses for the causes of ALS are reviewed in the first chapter by Rossi and coauthors. This chapter reviews the potential pathogenic mechanism involved in

The chapter by Shin and Lee reviews the cellular mechanisms found to potentially partici‐ pate in the degeneration of motor neurons in ALS. This chapter provides a cellular approach to the proposed mechanisms of motor neuron death in ALS, supporting the hypothesis that multiple molecular pathways could be involve in motor neuron death in different patients. Diamanti and collaborators provide further support for the hypothesis of multiple molecu‐ lar mechanisms in ALS by reviewing correlations between genotype and disease presenta‐ tion. Using studies of Italian ALS patients, the authors provide evidence showing the correlation between different phenotypic presentations of ALS with known genetic causes of

The chapter by Bowerman and collaborators reviews up to day evidence of the role of neu‐ roinflammation in the pathology of ALS. The role of astrocytes and other inflammatory cells is reviewed in detail. The authors also discuss in depth the possible inflammatory mediators

Franco and collaborators review the highly controversial participation of oxidative stress in the pathology of ALS. The chapter focuses on the oxidative mechanisms proposed to explain

Ferraiuolo and coauthors provide a new interpretations of the ALS literature based on the recent discovery that a plethora of new genetic mutations affecting a variety of genes are linked to ALS. The review provides an unique perspective on the strengths and weaknesses of classic and new animal models of the disease based on performance and similarities to

and molecular mechanism involved in the induction of motor neuron death.

the gain-of-function of ALS-linked mutant SOD.

the etiology of ALS providing short description of each mechanism.
