Laboratory of Molecular Medicine, Department of Surgery, Davis Heart & Lung Research Institute and The Ohio State University Medical Center, Columbus, Ohio 43210 USA
Address for correspondence: Dr. Chandan K. Sen, 512 Davis Heart & Lung Research Institute, 473 West 12th Avenue, The Ohio State University Medical Center, Columbus, Ohio 43210. Voice: 614-247-7786; fax: 614-247-7818. sen-1{at}medctr.osu.edu
Vitamin E is essential for normal neurological function. It
is the major lipid-soluble, chain-breaking antioxidant in the
body, protecting the integrity of membranes by inhibiting lipid
peroxidation. Mostly on the basis of symptoms of primary vitamin
E deficiency, it has been demonstrated that vitamin E has a
central role in maintaining neurological structure and function.
Orally supplemented vitamin E reaches the cerebrospinal fluid
and brain. Vitamin E is a generic term for all tocopherols and
their derivatives having the biological activity of RRR-
-tocopherol,
the naturally occurring stereoisomer compounds with vitamin
E activity. In nature, eight substances have been found to have
vitamin E activity:
-, ß-,
- and
-tocopherol; and
-, ß-,
- and
-tocotrienol. Often, the term vitamin
E is synonymously used with
-tocopherol. Tocotrienols, formerly
known as
,
, or
-tocopherols, are similar to tocopherols except
that they have an isoprenoid tail with three unsaturation points
instead of a saturated phytyl tail. Although tocopherols are
predominantly found in corn, soybean, and olive oils, tocotrienols
are particularly rich in palm, rice bran, and barley oils. Tocotrienols
possess powerful antioxidant, anticancer, and cholesterol-lowering
properties. Recently, we have observed that
-tocotrienol is
multi-fold more potent than
-tocopherol in protecting HT4 and
primary neuronal cells against toxicity induced by glutamate
as well as by a number of other toxins. At nanomolar concentration,
tocotrienol, but not tocopherol, completely protected neurons
by an antioxidant-independent mechanism. Our current work identifies
two major targets of tocotrienol in the neuron: c-Src kinase
and 12-lipoxygenase. Dietary supplementation studies have established
that tocotrienol, fed orally, does reach the brain. The current
findings point towards tocotrienol as a potent neuroprotective
form of natural vitamin E.
