Natural substances and neurodegenerative diseases: from molecular mechanisms to clinical effects

Symptoms of Alzheimer's disease (AD), the most common form of dementia and neurodegenerative disorders, begin with insidious loss of memory which progresses to involve all aspects of cognition, including confusion and mood swings.

The dilemma we face today is that the five drugs approved for Alzheimer's only partially treat some of the symptoms. None of them can slow or stop the progression of the disease itself. A vast array of published data, however, shows that proper use of nutrients, hormones, and other natural drugs may dramatically reduce one's risk of developing AD. Several natural compounds have ample research behind them demonstrating their ability to take aim at multiple steps in the development of neurodegenerative disorders. Among dietary antioxidants curcumin and Ginkgo biloba were extensively studied for their neuroprotective effects in AD. The rationale for this alternative therapeutic approach was based on several pre-clinical studies which suggested the neuroprotective effects especially for Ginkgo biloba, curcumin and resveratrol, due to either a free radical scavenging activity or stabilization of mitochondrial functions. Moreover, several lines of evidence show that fish oil supplementation could be one other preventive strategy we have against the disease. Furthermore, a plausible link between neurosteroids and neurodegenerative disorders, like AD, has been discussed. Endogenous neurosteroids (steroids that are synthesized within the nervous system) might have important roles in cognitive functions and normal aging is associated with several alterations in neurosteroid production and secretion. Particularly the neurosteroid allopregnanolone has recently shown promise in alleviating cognitive and neuronal sequelae of AD.

The aim of this lecture is to summarize the main pharmacologic features of natural substances as well as to underlie the main outcomes reached by clinical studies designed to demonstrate the efficacy of them in patients.