Abstract

Priyanshu Yogeshwar Chaudhari, *Prof. Suraj P. Rajurkar, Sakshi Banduji Deshmukh, Nikhil Rupchand Rathod, Prerna Shrikumar Deodhagale, Shruti P. Kadam

ABSTRACT

Ion channels are fundamental to neuronal excitability, synaptic transmission, and overall neurophysiological balance. Alterations in their function—whether due to genetic mutations, post- translational modifications, or pathological insults—are central to the onset and progression of numerous neurological disorders. This review discusses the physiological and pathological significance of four major classes of ion channels: sodium (Na?), potassium (K?), calcium (Ca²?), and chloride (Cl?). Sodium channel dysfunction contributes to excitotoxicity and neuronal hyperexcitability observed in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Potassium channel alterations disrupt neuronal repolarization and glial homeostasis, influencing neuroinflammation and excitability in PD, AD, and epilepsy. Aberrant calcium signaling through voltage-gated calcium channels mediates oxidative stress, excitotoxic damage, and glial activation, thereby exacerbating neurodegenerative processes. Finally, impaired chloride homeostasis—primarily due to altered KCC2 or NKCC1 function—leads to a loss of inhibitory control and increased network hyperexcitability in epilepsy and AD. Understanding the mechanisms underlying ion channel dysfunction provides crucial insights into neurodegenerative pathophysiology and highlights novel therapeutic strategies targeting ion channel modulation for the prevention and management of neurological diseases.