Doxorubicin induced aggregation of ?-synuclein: Insights into the mechanism of drug induced Parkinsonism

The aggregation of alpha-synuclein is a prominent feature of Parkinson's disease. It is induced by factors such as genetic mutations and presence of metal salts leading to Parkinson's like symptoms. Existing case studies show that patients undergoing cancer chemotherapeutics are also prone to developing Parkinson's like symptoms. However, the underlying cause behind onset of these symptoms is not understood. It is not clear whether the administration of chemotherapeutic drugs alter the structural stability of alpha-synuclein. In the present study, we address this question by looking into the effect of chemotherapeutic drug namely doxorubicin on the alpha-synuclein stability. Using complementary spectroscopic, molecular docking and imaging techniques, we observe that doxorubicin interacted with central aggregation prone region of alpha-synuclein and induces destabilization leading to aggregation. We also show that the combination of doxorubicin and L-DOPA drugs impedes the alpha-synuclein aggregation. This may explain the reason behind the effectiveness of using L-DOPA against Parkinson's like symptoms.

Automated summary

The aggregation of alpha-synuclein is a key characteristic of Parkinson's disease and is influenced by the chemotherapeutic drug doxorubicin. The study reveals that doxorubicin interacts with the aggregation-prone region of alpha-synuclein, destabilizing it and promoting aggregation. Additionally, the combination of doxorubicin and L-DOPA drugs inhibits alpha-synuclein aggregation.