Objective: This review explores the potential of optogenetics in Parkinson’s disease (PD) therapy, emphasizing its ability to address the limitations of current treatments like deep brain stimulation (DBS) and pharmacological interventions. It discusses findings from PD animal models, the synergy between optogenetics and DBS, and the technique’s role in advancing stem cell-based therapies.

Background: Current PD treatments, including levodopa and DBS, primarily manage symptoms without altering disease progression. Levodopa is associated with motor fluctuations, while DBS, despite its widespread use, is invasive and lacks specificity, often leading to off-target neurostimulation and strict eligibility criteria.

Optogenetics, an innovative approach combining gene therapy and light-based neuromodulation, enables precise neuronal control by introducing light-sensitive proteins into excitable cells (Fig. 1). Unlike DBS, optogenetics delivers targeted stimulation, affecting only neurons expressing these proteins and reducing off-target effects (Fig. 2). Advances in optical device technology suggest that optogenetics could evolve from a minimally invasive to a potentially noninvasive therapy.

Method: A comprehensive literature review.

Results: Optogenetics has demonstrated significant potential in PD by selectively modulating key neural circuits, such as the subthalamic nucleus (STN), globus pallidus externa (GPe), and striatal pathways. Preclinical studies show its ability to restore motor function, normalize pathological neural activity, and enhance dopamine release.

Moreover, integrating optogenetics with DBS has provided deeper insights into DBS mechanisms and uncovered novel therapeutic targets, including cortical somatostatin interneurons. Optogenetics has also advanced stem cell therapy by allowing precise control over transplanted cell activity and differentiation.

Despite its promise, several challenges remain, including efficient light delivery to deep brain structures and ethical considerations surrounding gene therapy in humans.

Conclusion: Optogenetics presents a transformative approach to PD treatment, addressing the limitations of existing therapies. Its integration with DBS and stem cell-based strategies offers the potential for long-lasting, disease-modifying effects. With continued advancements, optogenetics could become a cornerstone in the treatment of neurodegenerative disorders.

Mechanism of Action of Optogenetics

Specificity Profiles of DBS and Optogenetics

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