Purinergic P2X(7) Receptor: A Therapeutic Target in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by upper and lower motor neuron loss. The pathomechanisms of ALS are still poorly understood with current hypotheses involving genetic mutations, excitotoxicity, and reactive oxygen species formation. In the absence of a disease altering clinically approved therapeutic, there is an ever-increasing need to identify new targets to develop drugs that delay disease onset and/or progression. The purinergic P2X(7) receptor (P2X(7)R) has been implicated widely across the ALS realm, providing a potential therapeutic strategy. This review summarizes the current understanding of ALS, the P2X(7)R and its role in ALS, the current landscape of P2X(7)R antagonists, and the in vivo potential of these antagonists in preclinical ALS models.