Insight into the application of optogenetics for regulating motor-related circuits in Parkinson's disease and novel therapeutic target exploration

Abstract

Parkinson's disease (PD) is one of the most pervasive neurodegenerative diseases. However, the etiology and pathogenesis of PD have not been fully elucidated, the underlying neural circuits or neuron types have not been fully identified, and the roles that different neuronal subtypes in distinct deep brain nuclei play in the pathophysiological process of PD need to be explored. Optogenetics is a technique that can realize the exact temporal and spatial specific control of a defined neuron subpopulation, which may contribute to the comprehension of pathophysiological mechanism of PD. For this scoping review, we screened the PubMed database. We identified articles reporting researches explored the ways to ameliorate PD symptoms and its potential mechanism using optogenetic technology. This article reviews the application of optogenetic technology in the exploration of the pathogenesis of PD. The disequilibrium of neural activity within cortico-basal ganglia-thalamo-cortical (CBT) neural circuit circuits is closely related to the generation of PD. Moreover, these insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels. Optogenetics provides a specific cell type-targeted method for neuronal manipulation that is highly accurate for clarifying the pathogenesis of PD, developing related drug targets and exploring surgical treatment mechanisms, and providing a basis for neuromodulation target development. As an alternative type of gene therapy, optogenetics might also find future use in PD therapy, and novel genome-editing technology could also potentially be applied as individualized gene therapy for genetic types of PD.