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Published on: July 31, 2017
Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds
Christian Behl1, Bernd Moosmann
1Max-Planck-Institute of Psychiatry, Munich, Germany.
Abstract:
Many neurodegenerative disorders and syndromes are associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids, cytokines or synthetic drugs commonly share oxidative downstream processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. The pathophysiological role of ROS has been intensively studied in in vitro and in vivo models of chronic neurodegenerative diseases such as Alzheimer's disease (AD) and of syndromes associated with rapid nerve cell loss as occuring in stroke. In AD, oxidative neuronal cell dysfunction and cell death caused by protofibrils and aggregates of the AD-associated amyloid beta protein (Abeta) may causally contribute to pathogenesis and progression. ROS and reactive nitrogen species also take part in the complex cascade of events and the detrimental effects occuring during ischemia and reperfusion in stroke. Direct antioxidants such as chain-breaking free radical scavengers can prevent oxidative nerve cell death. Although there is ample experimental evidence demonstrating neuroprotective activities of direct antioxidants in vitro, the clinical evidence for antioxidant compounds to act as protective drugs is relatively scarce. Here, the neuroprotective potential of antioxidant phenolic structures including alpha-tocopherol (vitamin E) and 17beta-estradiol (estrogen) in vitro is summarized. In addition, the antioxidant and cytoprotective activities of lipophilic tyrosine- and tryptophan-containing structures are discussed. Finally, an outlook is given on the neuroprotective potential of aromatic amines and imines, which may comprise novel lead structures for antioxidant drug design.
Insights
Oxidative stress contributes to neurodegenerative diseases like Alzheimer's and stroke. Antioxidants show promise in preventing nerve cell death, but clinical evidence for their effectiveness as drugs is limited.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Neurodegenerative disorders, including Alzheimer's disease (AD) and stroke, are linked to excessive reactive oxygen species (ROS) and oxidative stress.
- Oxidative processes are common downstream pathways in nerve cell death induced by various neurotoxins, leading to acute destruction or apoptosis.
- While in vitro and in vivo models show the role of ROS in AD pathogenesis and stroke, clinical evidence for antioxidant drugs is scarce.
Purpose of the Study:
- To summarize the neuroprotective potential of antioxidant phenolic structures, such as alpha-tocopherol (vitamin E) and 17beta-estradiol (estrogen).
- To discuss the antioxidant and cytoprotective activities of lipophilic tyrosine- and tryptophan-containing compounds.
- To provide an outlook on novel lead structures for antioxidant drug design based on aromatic amines and imines.
Main Methods:
- Review of existing literature on the neuroprotective effects of antioxidants in vitro and in vivo models.
- Analysis of studies investigating phenolic structures, lipophilic amino acid derivatives, and aromatic amines/imines for antioxidant and cytoprotective properties.
- Focus on experimental evidence for preventing oxidative nerve cell death.
Main Results:
- Direct antioxidants, like free radical scavengers, can prevent oxidative nerve cell death in experimental models.
- Phenolic compounds (alpha-tocopherol, 17beta-estradiol) exhibit neuroprotective potential in vitro.
- Lipophilic tyrosine- and tryptophan-containing structures demonstrate antioxidant and cytoprotective activities.
Conclusions:
- Antioxidants show significant neuroprotective potential in experimental models of neurodegenerative diseases.
- Despite promising in vitro results, clinical translation of antioxidant compounds as neuroprotective drugs remains a challenge.
- Aromatic amines and imines represent potential novel lead structures for the development of antioxidant drugs for neuroprotection.
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