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

• Published in: Neuropharmacology Vol. 169; p. 107461
• Main Authors: Shrivastava, Amulya Nidhi, Triller, Antoine, Melki, Ronald
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2020; Elsevier
• Subjects: Alzheimer's disease; ATP1A3 disorders; Life Sciences; Na+/K+-ATPase; neurodegeneration; Neurons and Cognition; Parkinson's disease; neurodegeneration; Parkinson's disease; Na+/K+-ATPase; Alzheimer's disease; ATP1A3 disorders; Na(+)/K(+)-ATPase
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2018.12.008

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 α3-subunit containing Na+/K+-ATPase expression is restricted to neurons. Heterozygous mutations within α3-subunit leads to Rapid-onset Dystonia Parkinsonism, Alternating Hemiplegia of Childhood and other neurological and neuropsychiatric disorders. Additionally, proteins such as α-synuclein, amyloid-β, tau and SOD1 whose aggregation is associated to neurodegenerative diseases directly bind and impair α3-Na+/K+-ATPase activity. The review will provide a summary of neuronal α3-Na+/K+-ATPase functional properties, expression pattern, protein-protein interactions at the plasma membrane, biophysical properties (distribution and lateral diffusion). Lastly, the role of α3-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’. •The low Na+ affinity α3 is a neuron specific subunit of Na+/K+-ATPase.•α3-Na+/K+-ATPase laterally diffuses and form clusters on the plasma membrane.•Over 90 mutations affect the gene encoding for α3-Na+/K+-ATPase (ATP1A3).•α3-Na+/K+-ATPase interacts with exogenous α-Synuclein and Amyloid-β.