A step in the ALS direction: lessons from the purinome.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is the most common form of motor neuron disease and results in the loss of upper and lower motor neurons leading to loss of muscle function and culminating in death. In addition, patients frequently exhibit extra-motor deficits and suffer from comorbid psychiatric symptoms, including frontotemporal dementia. There are no effective treatments or reliable biomarkers for this disease. Emerging evidence indicates complex roles for members of the purinome, a network of ecto-enzymes, release pathway and cell-surface receptors involving ATP, adenosine and other nucleotides in ALS. This chapter will discuss ALS from the viewpoints of patients, clinicians and researchers, before providing brief overviews of ALS, the genes associated with this disease and the key mechanisms involved, namely neurodegeneration, muscle denervation atrophy, neuroinflammation and proteostasis dysfunction. In addition, this chapter will review the role of the purinome in ALS, with a focus on ectonucleotidases, ATP release pathways, P1 (adenosine) receptors, and P2X and P2Y receptors. This chapter will conclude by discussing future perspectives.