Unveiling the role of Na⁺/K⁺-ATPase pump: neurodegenerative mechanisms and therapeutic horizons.

Abstract

Sodium and potassium-activated adenosine 5'-triphosphatase (Na+/K+-ATPase) is a pivotal plasma membrane enzyme involved in neuronal activity and cellular homeostasis. The dysregulation of these enzymes has been implicated in a spectrum of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and neurodevelopmental disorders including autism spectrum disorder (ASD), psychiatric disorders such as schizophrenia, and neurological problems like epilepsy. A hallmark of these disorders is the gradual loss of neuronal integrity and function, often exacerbated by protein accumulation within brain cells. This review delves into the multifaceted role of Na⁺/K⁺-ATPase dysfunction in driving oxidative stress, excitotoxicity, and neuroinflammation, contributing to synaptic and neuronal damage. Emerging therapeutic strategies, such as gene therapy and developing isoform-specific enzyme modulators, offer promising avenues for targeted interventions. Furthermore, this review highlights innovative research directions, including the role of Na⁺/K⁺-ATPase in synaptic plasticity, the identification of endogenous regulators, and its contribution to neuroinflammatory pathways. Personalized medicine and advanced gene-editing technologies are positioned as transformative tools for crafting safer and more precise therapies tailored to individual patients. This comprehensive exploration underscores the enzyme's therapeutic potential and sets the stage for developing novel targeted strategies to mitigate the burden of Na⁺/K⁺-ATPase-linked neurological disorders.