Targeting Oxidative Stress in Parkinson's Disease with Multi-Target Compounds

Dear Colleagues,

Parkinson’s disease (PD) is an incurable and progressive neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra, resulting in dopamine deficiency. While extensive research and considerable advances have been made towards a better understanding of PD, the underlying cause remains a mystery. The research to date has revealed a highly complex pathogenesis of the disease with multiple genetic and environmental contributory factors. Nevertheless, there is compelling evidence to suggest that the early events involving oxidative stress represent a key factor in the complex degeneration cascade in PD. Biochemical alterations in the substantia nigra and the frontal cortex in preclinical PD include altered oxidative stress responses, such as reduced glutathione levels, increased neuroketals, and the lipoxidative damage of a-synuclein, indicating that oxidative damage occurs in the very early stages of the disease preceding the formation of Lewy bodies. The presence of enzymes that produce reactive oxygen species (ROS), such as monoamine oxidases (MAO), renders dopaminergic neurons particularly vulnerable to oxidative stress. Another factor that has been demonstrated to play a critical role in Parkinson's disease is iron dyshomeostasis, which leads to increased oxidative stress via the generation of highly damaging hydroxyl radicals. However, the current method of treatment is primarily focused on symptomatic relief, based on drugs that aim to restore the dopamine levels. The search for treatments for multifactorial diseases such as PD has resulted in a paradigm shift in drug development from the previously 'one-molecule, one-target' approach to the alternative and more promising multi-target-directed ligand (MTDL) approach, which has been successfully employed for the development of a growing number of new drugs over the last decade. 

The current Special Issue invites researchers to contribute original papers investigating the development of new multi-target drugs for the treatment of Parkinson’s disease, placing a special emphasis on their antioxidant activity as a property intended to mitigate the sources of oxidative stress through various mechanisms.  

Prof. Dr. Denitsa Yancheva
Dr. Neda Anastassova
Guest Editors

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