The role of the P2X7 receptor in the progression of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late‐onset and rapidly progressive neurodegenerative disease in humans, which is characterised by the degeneration and loss of motor neurons, eventually leading to paralysis and death. A similar disease phenotype can occur in dogs and is induced in transgenic mutant superoxide dismutase 1 (SOD1) mouse models. The mechanisms underlying neurodegeneration and disease progression are unknown, with evidence for the involvement of a wide range of cellular mechanisms. These include microglial activation, neuroinflammation, and aberrant release and uptake of toxic proteins such as mutant SOD1. P2X7, a purinergic receptor expressed in a range of central nervous system cells, is involved in inflammatory signalling pathways and is up‐regulated during ALS. Given this, the work presented in this thesis aimed to further examine P2X7 in the context of neurodegeneration, and investigate whether this receptor plays a role in ALS progression.