Glutamate in Amyotrophic Lateral Sclerosis: An Ageless Contestant

Since the seminal research that in the early 1990s determined that ALS patients have augmented levels of glutamate in the cerebral spinal fluid bathing the brain and spinal cord, glutamatergic excitotoxicity has been investigated in Amyotrophic Lateral Sclerosis (ALS). It is believed that an altered glutamate homeostasis is one mechanism underlying ALS. Indeed, plenty of evidence points to glutamate as a harmful factor in ALS, without disregarding the fact that the first and so far only approved treatment for ALS is riluzole, a drug that modulates glutamate. Hence in this chapter, we will discuss the effects of its excessive overload on neuronal homeostasis in ALS. Its association with toxic events includes Ca2+ overload, reactive oxygen species production, mitochondrial dysfunctions, and reactive gliosis. All linked to the development of ALS.