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Free radicals in Alzheimer's dementia: currently available therapeutic strategies
1Psychiatric Department, University of Würzburg, Federal Republic of Germany.
Abstract:
Substantial evidence now exists that oxidative stress may play an important role in the etiopathogenesis of DAT. The different sources of oxidative stress in DAT are suggesting several pharmacological opportunities for influencing the disease. It is possible to distinguish 2 major types of possible therapeutic agents according to their pharmacological point of attack. 1. Radical scavengers, agents directly interacting with free radicals. Candidates of this type are gingko biloba, vitamins A, C, E and estrogen. 2. Antioxidants, which are able to prevent or decrease the production of free radicals by use of specific neuropharmacological properties. Candidates are selegiline, a MAO-B inhibitor well established in the therapy of Parkinson's disease, and tenilsetam, which is believed to be an AGE-inhibitor. Recent in vitro studies have demonstrated the efficacy of both types of therapeutic agents by preventing or delaying oxidative neural damage. Some clinical data exist regarding the antidementive properties particularly in terms of gingko biloba, selegiline and vitamin E. The efficacy studies about these compounds seem to indicate a promising future strategy in the therapy of DAT. But it is too early to draw definite conclusions since it is well known that all of our candidate substances do not act specifically as radical scavengers or antioxidants.
Insights
Oxidative stress contributes to dementia of the Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
- Oxidative Stress Research
Background:
- Oxidative stress is implicated in the development of dementia of the Alzheimer's type (DAT).
- Identifying sources of oxidative stress in DAT suggests potential therapeutic targets.
Purpose of the Study:
- To explore pharmacological strategies for treating DAT by targeting oxidative stress.
- To review potential therapeutic agents, categorizing them as radical scavengers or antioxidants.
Main Methods:
- Review of existing evidence on oxidative stress in DAT.
- Categorization of potential therapeutic agents based on their mechanism of action.
- Analysis of in vitro and clinical data for candidate compounds.
Main Results:
- Two main classes of agents identified: radical scavengers (e.g., Ginkgo biloba, vitamins A, C, E, estrogen) and antioxidants (e.g., selegiline, tenilsetam).
- In vitro studies confirm the efficacy of both types in preventing oxidative neural damage.
- Preliminary clinical data suggest antidementive properties for Ginkgo biloba, selegiline, and vitamin E.
Conclusions:
- Therapeutic agents targeting oxidative stress show promise for DAT treatment.
- Further research is needed as candidate substances may have multiple mechanisms of action.
- Definitive conclusions on efficacy await more comprehensive clinical trials.