Application and research progress of tissue clearing techniques in Parkinson’s disease

Parkinson’s disease (PD), a prevalent neurodegenerative disorder, exhibits a rising global incidence. It severely impairs patients’ quality of life and imposes a significant burden on both society and families. However, despite considerable efforts and corresponding research achievements by numerous researchers both domestically and internationally, a specific treatment for PD remains elusive to date. The reason for this may lie in the complex pathogenesis of PD and the insufficient understanding of the abnormal neural networks in PD patients. Traditional research methods, such as two-dimensional histology, are limited in their observational scope and perspective, making it difficult to present a comprehensive pathological picture of PD. Therefore, breaking through the limitations of two-dimensional imaging to achieve three-dimensional pathological visualization holds significant importance for investigating PD’s mechanisms and developing precise treatments. In recent years, the application of tissue clearing techniques in the central nervous system has represented a major breakthrough in neuroscience research. This technique enables the observation of intrinsic cells and molecular structures within tissues in three dimensions without disrupting their architecture. It allows visualization of the structural basis of abnormal neural networks in PD, such as aberrant neurons or glial cells. Combined with optical imaging, tissue clearing facilitates three-dimensional reconstruction of neural circuits, thereby mapping the complex architecture of neural networks with greater accuracy. This approach provides deeper insights into the pathological neural networks in PD, opening up new perspectives and methodologies for its investigation. This review systematically summarizes the imaging principles of tissue clearing techniques, its advantages over traditional pathological techniques, and its applications in PD research—specifically its advancements in studying dopaminergic neurons, neural circuits, and α-synuclein. It concludes with future prospects for this technology in the PD field, aiming to provide a comprehensive theoretical foundation and technical reference for in-depth PD research and the development of effective therapies.