Cell biology and dynamics of Neuronal Na+/K+-ATPase in health and diseases

Neuronal Na+/K(+-)ATPase is responsible for the maintenance of ionic gradient across plasma membrane. In doing so, in a healthy brain, Na+/K+-ATPase activity accounts for nearly half of total brain energy consumption. The alpha 3-subunit containing Na+/K+-ATPase expression is restricted to neurons. Heterozygous mutations within alpha 3-subunit leads to Rapid-onset Dystonia Parkinsonism, Alternating Hemiplegia of Childhood and other neurological and neuropsychiatric disorders. Additionally, proteins such as alpha-synuclein, amyloid-beta, tau and SOD1 whose aggregation is associated to neurodegenerative diseases directly bind and impair alpha 3-Na+/K+-ATPase activity. The review will provide a summary of neuronal alpha 3-Na+/K+-ATPase functional properties, expression pattern, protein-protein interactions at the plasma membrane, biophysical properties (distribution and lateral diffusion). Lastly, the role of alpha 3-Na+/K+-ATPase in neurological and neurodegenerative disorders will be discussed. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'.