Introduction

The invention concerns novel compounds and their use as Parkinson’s disease-modifying agents. These new molecules significantly reduce the formation of Parkinson’s toxic aggregates and re-establish the functional interaction between alpha-synuclein and Synapsin III.

Technical features

The formation of alpha-synuclein insoluble aggregates is considered an early event that leads to dopaminergic neurons degeneration and formation of Lewy bodies in Parkinson’s Disease (PD). Synapsin III is a post-synaptic protein that coordinates, together with alpha-synuclein, the release of dopamine in healthy neurons. In PD instead, Synapsin III contributes to alpha-synuclein aggregation thus promoting its toxicity. The alpha-synuclein/Synapsin III pathological complex is therefore a novel promising therapeutic target for PD. Methylphenidate (MPH), a compound currently used for other diseases, can improve dopaminergic neurotransmission by promoting the functional alpha-synuclein/Synapsin III interaction instead of the pathological one. With our invention, we designed and synthesized novel compounds, structurally related to MPH, able to efficiently reduce alpha-synuclein aggregation by stimulating its functional interaction with Synapsin III. Such novel compounds have stronger efficacy than MPH as Parkinson’s disease-modifying agents.

Possible Applications

• Treatment of Parkinson’s Disease.

Advantages

• A more powerful molecule with respect to MPH;
• Potential regression of Parkinson’s toxic aggregates;
• Promotion of the non-pathologic functionality of the target.