Small Molecules, α-Synuclein Pathology, and the Search for Effective Treatments in Parkinson’s Disease

Summary

This narrative review examines how small molecules of intermediary metabolism and other compounds interact with misfolded α-synuclein to regulate its aggregation in Parkinson's disease. The authors synthesise evidence on dopamine, levodopa, glutathione redox states, and micronutrients (thiamine and β-hydroxybutyrate), proposing that the latter two micronutrients may work synergistically to slow or reverse neuronal α-synuclein pathology. The analysis suggests these molecular interactions may inform rational development of future therapeutic approaches.

Regional applicability

The findings are relevant to UK clinical practice and drug development for Parkinson's disease management, though translation would require clinical trial validation. UK healthcare policy and neurology guidelines may need to consider micronutrient supplementation strategies if clinical evidence strengthens.

Key measures

Mechanisms of α-synuclein folding and aggregation; interactions with dopamine, levodopa, reduced glutathione, oxidised glutathione, thiamine, and β-hydroxybutyrate; molecular pathways in neurodegeneration

Outcomes reported

The review synthesises current knowledge on interactions between α-synuclein and small molecules of intermediary metabolism and other natural and synthetic compounds that regulate α-synuclein aggregation. The authors propose that β-hydroxybutyrate and thiamine may have synergistic therapeutic potential in halting or reversing Parkinson's disease progression.

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