The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis

Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H(2)S) in the Central Nervous System (CNS) have changed. Consequently, H(2)S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H(2)S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H(2)S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.