Rockefeller Neuroscience Institute, Rockville MD, USA
CNR, Institute of Neurological Sciences, Catania, Italy

Spices of life: curcumin and other polyphenols as preventive agents against brain aging and neurodegenerative disorders.

One of the most prominent current theories of aging is the “free radical theory.” According to this theory, free radical molecules generated through mitochondrial metabolism can act as causative factor of abnormal function and cell death. Various toxins in the environment can injure mitochondrial enzymes, leading to increased generation of free radicals and oxidative stress, that over the life-span would eventually play a major role in aging. Free radical’s oxidative damage to key intracellular targets such as DNA or proteins has been shown to be a major cause of the degenerative diseases related to aging such as cancer and Alzheimer’s disease. Luckily, mammalian cells have developed highly protective systems against including oxidative challenges over time. When properly activated, each one of these cell systems has the possibility to restore cellular homeostasis and resume the ability to fight off oxidation. Activation of antioxidant pathways is particularly important for tissue with relatively weak antioxidant defenses, such as the brain. In fact, increasing evidence points to the notion that reduced cellular expression and activity of antioxidant proteins and the consequent oxidative stress are fundamental causes for brain aging processes and neurodegenerative diseases.
There are a variety of genes encoding proteins that possess anti-oxidant properties. Of particular interest in the central nervous system (CNS) is the hemeoxygenase-1 (HO-1), which has been reported to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge. At the same time, a number of studies have supported the beneficial effects of some commonly used natural products in preventing various pathologic conditions. Spices and herbs often contain phenolic substances with potent antioxidative and chemopreventive properties. Among them is curcumin, a natural phenolic agent, extracted from the rhizome of Curcuma Longa, and the yellow pigment in curry, strongly induced HO-1 expression and activity in rat astrocytes. In recent years, there has been an unprecedented interest in identifying new pharmacological strategies to increase defense mechanisms by activating multiple antioxidant defense genes, a process that has been referred to as programmed cell life. Previous studies have shown that induction of HO-1 can represent an efficient antioxidant system and a potential pharmacological target in a variety of oxidant- and inflammatory-mediated diseases, including brain aging and neurodegenerative disorders. Our research extends previous findings examining the neuroprotective effects of curcumin and other close polyphenols. This study identifies a novel class of compounds that could be used for therapeutic purposes as preventive agent against acute neurodegenerative conditions that affect an increasingly aged population.