FAST BREAKING PAPERS
Russel J. Reiter talks with
ScienceWatch.com and answers a few questions about
this month's Fast Breaking Paper in the field of Biology
& Biochemistry. The author has also sent along images
of their work.
Field: Biology & Biochemistry
Article Title: One molecule, many derivatives: A
never-ending interaction of melatonin with reactive oxygen
and nitrogen species?
Authors: Tan, DX;Manchester, LC;Terron, MP;Flores,
Journal: J PINEAL RES
Year: JAN 2007
* Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct
Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
* Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct
Biol, San Antonio, TX 78229 USA.
(addresses may have been truncated; see full
Why do you think the paper is highly
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
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
Where do you see your research leading in the
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
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
Russel J. Reiter, Ph.D., Dr.h.c.mult.
Department of Cellular and Structural Biology
The University of Texas Health Science Center
San Antonio, TX, USA