Progress in the study of ion channel function, mechanisms, and mathematical modeling in Parkinson’s disease

Parkinson's disease is a progressive neurodegenerative disorder in which ion channel dysfunction significantly contributes to the pathophysiology. This review summarizes recent advancements in the altered functions of voltage-gated sodium, potassium, and calcium channels, together with ligand-gated channels, revealing how these abnormalities disrupt neuronal excitability, synaptic transmission, autophagy, and metal ion homeostasis. Complementary mathematical modeling, ranging from Hodgkin-Huxley-type simulations of neuronal electrical activity to large-scale network dynamics and data-driven integrative frameworks, successfully reproduces experimental observations and predicts disease progression. These combined experimental and computational insights facilitate the development of targeted therapeutic strategies, including ion channel modulators and neuroprotective agents. By identifying key mechanistic links and overcoming current limitations in model complexity and data integration, this work underscores the importance of multidisciplinary collaboration among neuroscience, pharmacology, and computational biology to advance precise, channel-directed treatments for Parkinson's disease.