FAST BREAKING PAPERS

Why do you think the paper is highly cited?

This report summarizes the recently discovered multiple actions whereby melatonin and its metabolites (Fig. 1) protect cells and organs from the molecular damage meted out by free radicals and related toxic molecules. This damage, conventionally referred to as oxidative stress, contributes to many diseases and is considered to be a major cause of many degenerative changes associated with aging.

The diverse mechanisms by which melatonin and its by-products work to prevent molecular damage set it apart from other antioxidants, especially within the brain. The process by which melatonin and its metabolites sequentially neutralize toxic reactants is referred to as the antioxidant cascade. This cascade of reactions, coupled with melatonin’s ability to act via receptor-mediated mechanisms to stimulate the activity of antioxidative enzymes and promote the efficient flow of electrons through the mitochondrial electron transport chain, makes it superior to conventional antioxidants, especially in vivo.

Another fact that makes melatonin of great interest is that every living creature seems to produce it, i.e., many plants and all animals from one-celled organisms through humans. This widespread distribution portends important functions for this molecule.

Does it describe a new discovery, methodology, or synthesis of knowledge?

This article is a synthesis and integration of a large body of newly uncovered information related to melatonin that has accumulated essentially within the last five years. New facts about this highly beneficial molecule are being discovered almost daily. Its potential utility in clinical medicine is rapidly attracting the attention of scientists/physicians.

Would you summarize the significance of your paper in layman’s terms?

Melatonin is a beneficial and protective molecule that is abundantly produced in the body when we are young. As we age, its production wanes (Fig. 2). The drop in melatonin may contribute to the progressive decline in bodily functions during aging. Additionally, its reduction may contribute to the onset, progression, or severity of a number of serious, degenerative diseases normally found in the older population.

For example, in experimental animal models of diseases, including stroke (Fig. 3), heart attack, Alzheimer’s disease, Parkinsonism, and other degenerative processes of aging, melatonin has proven beneficial. Also, melatonin is an excellent protector against the damaging effects of ionizing radiation. Its presence in plants has implications for nutrition and phytoremediation. Clearly, there are many situations in which melatonin will be useful.

How did you become involved in this research and were there any problems along the way?

While my research group has had many years of research experience investigating melatonin, almost serendipitously, we only discovered it to be a powerful antioxidant and highly protective against free radical damage a little over a decade ago. As with many truly novel and revolutionary discoveries, many scientists initially doubted its function in protecting against oxidative stress.

Fortunately, scientific truth has a habit of identifying itself with imaginative studies which have now been performed by many scientists. Currently, the evidence that melatonin protects against oxidative damage is no longer disputed. In the last three to four years, because of its multiple beneficial actions, interest in melatonin has increased exponentially.

Where do you see your research leading in the future?

Although the basic research is not yet complete, since melatonin has very low toxicity, is inexpensive, and has many potential benefits, it is being tested with increased frequency at the clinical level. The publications of the results of a number of ongoing clinical trials are anticipated in the next several years.

While basic research on its benefits will aggressively continue, more studies at the clinical level are being planned and getting underway. Unfortunately, what makes melatonin of interest, i.e., naturally occurring, low toxicity, non-patentable, inexpensive—is also a major drawback. Unless a compound has a high likelihood of providing a substantial financial return, enthusiasm for the molecule by industry is low. Thus, whereas melatonin has been found to be a highly beneficial molecule, it is generally ignored by the pharmaceutical industry.

Are there social or political implications for your research?

Melatonin has the potential to be a significant molecule to protect against diseases and aging processes where free radical damage is a contributing factor. There are many diseases in which oxidative damage has been implicated as being causative. This is particularly valid for diseases related to aging. This becomes of paramount importance because the population of many countries is becoming progressively older. This being the case, debilitating diseases of aging will surely become more prominent unless science can identify the means of deferring these degenerative changes. Melatonin may be one molecule that can assist in achieving this goal.

Russel J. Reiter, Ph.D., Dr.h.c.mult.
Professor
Department of Cellular and Structural Biology
The University of Texas Health Science Center
San Antonio, TX, USA