Mechanism of cuproptosis in pathogenesis of Parkinson’s disease

Parkinson’s disease is a high prevalent neurodegenerative disease. The exact pathogenesis of this disease remains to be fully elucidated; however, regardless of the underlying mechanisms, the ultimate outcome is the progressive loss of dopaminergic neurons. Cuproptosis is a recently discovered form of copper-induced regulated cell death. Its morphology, biochemical properties, and mechanism of action differ from known forms of cell death such as apoptosis, autophagy, necrosis, and pyroptosis. Copper binds to the lipoylated components of the tricarboxylic acid cycle, causing proteotoxic stress, which eventually results in cell cuproptosis. The pathological biochemical hallmarks of Parkinson’s disease include mitochondrial dysfunction and lower brain levels of copper and glutathione. These processes are intricately associated with the underlying mechanism of cuproptosis. However, the specific aspects of the interplay between the pathogenesis of Parkinson’s disease and cuproptosis have yet to be fully explored. The article summarizes the available evidence on cuproptosis as the cause of neuronal death in Parkinson’s disease, and its role in the pathogenesis of Parkinson’s disease. Cuproptosis offers a novel and promising approach to understanding the role of copper dysregulation in the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the mechanisms underlying copper-induced cell death will facilitate the development of novel therapeutic strategies, particularly to address medical conditions associated with copper imbalance, including Wilson’s disease and Parkinson’s disease. The therapeutic potential of targeting cuproptosis using copper chelation strategies has already been confirmed in various experimental models that demonstrate significant improvement in cognitive functions and symptoms of the disease. The incorporation of the concept of cuproptosis into clinical practice promises to enhance diagnostic accuracy and treatment efficacy by personalizing medical approaches, facilitating early intervention, and enabling precise regulation of copper levels. The further investigation of the complex molecular mechanisms of cuproptosis, the development of specific biomarkers for the early detection of neurodegenerative diseases, and the optimization of therapeutic protocols to ensure the safety and efficacy of treatment are all essential. Addressing these challenges will play a pivotal role in the successful integration of novel scientific advances into clinical practice, thereby enhancing patient care and overall quality of life.