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

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 3303

Special Issue Editors


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Guest Editor
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 9, 1113 Sofia, Bulgaria
Interests: modulation of oxidative stress; radical scavenging mechanisms; synthesis of pharmacologically active compounds; DFT calculations; IR spectroscopy

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Guest Editor
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Building 9, 1113 Sofia, Bulgaria
Interests: neurodegenerative disorders drug-development; organic synthesis of pharmacologically active compounds; antioxidant activity; Parkinson's disease; Alzheimer's disease; multi-target directed ligands; hybrid compounds; MAO-B inhibitors

Special Issue Information

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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Published Papers (2 papers)

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Review

20 pages, 687 KiB  
Review
Food and Food Waste Antioxidants: Could They Be a Potent Defence against Parkinson’s Disease?
by Claudia Cannas, Giada Lostia, Pier Andrea Serra, Alessandra Tiziana Peana and Rossana Migheli
Antioxidants 2024, 13(6), 645; https://doi.org/10.3390/antiox13060645 - 25 May 2024
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Abstract
Oxidative stress, an imbalance between reactive oxygen species (ROS) and endogenous antioxidants, plays an important role in the development of neurodegenerative diseases, including Parkinson’s. The human brain is vulnerable to oxidative stress because of the high rate of oxygen that it needs and [...] Read more.
Oxidative stress, an imbalance between reactive oxygen species (ROS) and endogenous antioxidants, plays an important role in the development of neurodegenerative diseases, including Parkinson’s. The human brain is vulnerable to oxidative stress because of the high rate of oxygen that it needs and the high levels of polyunsaturated fatty acids, which are substrates of lipid peroxidation. Natural antioxidants inhibit oxidation and reduce oxidative stress, preventing cancer, inflammation, and neurodegenerative disorders. Furthermore, in the literature, it is reported that antioxidants, due to their possible neuroprotective activity, may offer an interesting option for better symptom management, even Parkinson’s disease (PD). Natural antioxidants are usually found in several foods, such as fruits, vegetables, meat, fish, and oil, and in food wastes, such as seeds, peels, leaves, and skin. They can help the system of endogenous antioxidants, protect or repair cellular components from oxidative stress, and even halt lipid, protein, and DNA damage to neurons. This review will examine the extent of knowledge from the last ten years, about the neuroprotective potential effect of natural antioxidants present in food and food by-products, in in vivo and in vitro PD models. Additionally, this study will demonstrate that the pool of dietary antioxidants may be an important tool in the prevention of PD and an opportunity for cost savings in the public health area. Full article
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31 pages, 2455 KiB  
Review
Targeting the Cysteine Redox Proteome in Parkinson’s Disease: The Role of Glutathione Precursors and Beyond
by Marcos A. Martinez-Banaclocha
Antioxidants 2023, 12(7), 1373; https://doi.org/10.3390/antiox12071373 - 30 Jun 2023
Cited by 2 | Viewed by 1990
Abstract
Encouraging recent data on the molecular pathways underlying aging have identified variants and expansions of genes associated with DNA replication and repair, telomere and stem cell maintenance, regulation of the redox microenvironment, and intercellular communication. In addition, cell rejuvenation requires silencing some transcription [...] Read more.
Encouraging recent data on the molecular pathways underlying aging have identified variants and expansions of genes associated with DNA replication and repair, telomere and stem cell maintenance, regulation of the redox microenvironment, and intercellular communication. In addition, cell rejuvenation requires silencing some transcription factors and the activation of pluripotency, indicating that hidden molecular networks must integrate and synchronize all these cellular mechanisms. Therefore, in addition to gene sequence expansions and variations associated with senescence, the optimization of transcriptional regulation and protein crosstalk is essential. The protein cysteinome is crucial in cellular regulation and plays unexpected roles in the aging of complex organisms, which show cumulative somatic mutations, telomere attrition, epigenetic modifications, and oxidative dysregulation, culminating in cellular senescence. The cysteine thiol groups are highly redox-active, allowing high functional versatility as structural disulfides, redox-active disulfides, active-site nucleophiles, proton donors, and metal ligands to participate in multiple regulatory sites in proteins. Also, antioxidant systems control diverse cellular functions, including the transcription machinery, which partially depends on the catalytically active cysteines that can reduce disulfide bonds in numerous target proteins, driving their biological integration. Since we have previously proposed a fundamental role of cysteine-mediated redox deregulation in neurodegeneration, we suggest that cellular rejuvenation of the cysteine redox proteome using GSH precursors, like N-acetyl-cysteine, is an underestimated multitarget therapeutic approach that would be particularly beneficial in Parkinson’s disease. Full article
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