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7458959 
Book/Book Chapter 
Antioxidant Therapy and Neurodegenerative Disorders: Lessons From Clinical Trials 
Silva, C; Pinto, M; Fernandes, C; Benfeito, S; Borges, F 
2021 
Academic Press 
Oxford 
Systems Medicine 
97-110 
Central nervous system (CNS) diseases, such neurodegenerative disorders (NDs) are increasing over the last years as a consequence of a continuous growing of the life expectancy and aging of population. The molecular mechanisms underlying the pathophysiology of NDs are still not fully understood. Neurodegeneration seems to be multifactorial and associated to a complex set of events comprising oxidative stress, inflammation, protein dysfunction and aggregation, among others, that at the end lead to the demise of neurons. It has been advocated that oxidative stress induced by imbalanced redox states, involving either overproduction of reactive species or dysfunction of the antioxidant system, and the higher levels of iron in the brain has a crucial role in NDs progression. Therefore, antioxidant therapy emerged as a useful approach to modulate oxidative stress events. However, despite the promising results obtained in in vitro cell-free and cell-based assays, the pharmacokinetics/pharmacodynamics properties of the majority of antioxidants preclude their advance in pre- and clinical trials. In this chapter the nonenzymatic endogenous and exogenous antioxidants (single and combined antioxidant therapy) currently in clinical trials, as drugs or supplements, for treatment of NDs will be highlighted. From the data one can conclude that the clinical trials performed so far related with single or combined antioxidants are still in a very early stage. So, a huge research space in the antioxidant field remains to be explored that hopefully will yield new and effective neuroprotective agents in a foreseeable future. 
Antioxidants; Clinical trials; Neurodegenerative disorders; Neuroprotection; Oxidative stress; Pharmacotherapy 
Wolkenhauer, Olaf