Neurology Central

Natural antioxidants in hybrids for the treatment of neurodegenerative diseases: a successful strategy?

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It is well established that oxidative stress is one of the characteristics of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease [1]. Free radicals, that is, reactive oxygen species (ROS) and reactive nitrogen species, are damaging a variety of biomolecules like lipids, proteins and DNA. Such radicals are generated in the pathology of neurodegenerative diseases and eventually lead to neuronal cell death. They contribute to the overall pathophysiology and pathogenesis of these diseases, but are not their sole cause. In fact, it is unclear until now at which stage of the pathophysiological cascades oxidative stress occurs. Irrespective of the stage though, it is obvious that ROS enhance if not multiply the effects of the neuropathological cascades [1].
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In AD, for example, pathological mechanisms mainly include hyperphosphorylation of T proteins, reduction of acetylcholine receptor levels, mitochondrial dysfunction, neuronal DNA damage, cerebral glucose hypometabolism, aggregation of β-amyloid peptides (Aβ) and oxidative stress [1,2]. With several mechanisms contributing to a complex pathological network, development of therapeutically applicable drugs is extremely challenging. A drug addressing only one biological target is probably not going to yield any success in stopping neurodegenerative diseases. Therefore, multitarget or hybrid drugs – combining two or more pharmacologically active units – that are capable of modifying several biological targets, may overcome the shortcomings of a single-target drug.

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