DESCRIPTIONS

After the development of deprenyl, in 1960s, Professor Joseph Knoll opened up a new area of research in the 1970s with his discovery of what he referred to as “enhancer-sensitiveregulations in the mammalian brain.”Hedefined “enhancer-sensitive brain regulation” as the capability of the brain to shift to work on a higher activity level in milliseconds in need and attributed this capability to the release of a natural substance, he referred to an “enhancer.” In this book, Knoll presents some findings which led him to postulate the operation of enhancer-sensitive brain regulations. Subsequently, the presentation is centered on enhancer-sensitive brain regulation and aging and the possible use of synthetic enhancers to slow down the aging process. Instrumental to this research was his demonstration that during the developmental/young phase of life, from weaning until sexual maturity, enhancer-sensitive neurons work on a significantly higher activity level than before or later. Then in the post-developmental/aging phase, there is a slow, irresistible decline of enhancer-sensitive brain regulations, that continues until death. The development of synthetic enhancers rendered the countering of brain-aging possible. Knoll emphasizes the importance of recognizing that the regressive effect of brain aging in mammals is primarily due to the age-related decline of natural enhancer regulation. Knoll identified β-phenylethylamine (PEA) for the catecholaminergic neurons and tryptamine for the serotonergic neurons as natural enhancers. The development of selegiline/(-)-deprenyl (DEP), the PEA-derived synthetic catecholaminergic activity enhancer (CAE), and BPAP, the tryptamine-derived synthetic serotonergic activity enhancer catalyzed the discovery of the unique ability of synthetic enhancers to prevent brain-aging. DEP, was described first as the selective inhibitor of MAO-B enzyme and it has been known since 1988 that mammals treated with DEP, live significantly longer than their saline treated peers. Knoll also showed that the enhancer-sensitive catecholaminergic neurons in rats treated from sexual maturity until death with BPAP kept their unchanged learning ability. In another line of research related to aging Knoll and his associates had shown that administration of a low dose of BPAP, from sexual maturity throughout life fully prevented aging of the dopaminergic neurons. The findings showed that the slowly progressing, aging-related loss of dopamine, a natural enhancer, is responsible for the regressive effects of brain aging.It has been calculated that in a healthy human population, the loss of striatal dopamine (DA) is about 40% at the age of 75. Pursuing further this line of research it was shown that substituting the natural enhancer with a synthetic enhancer has become a distinct possibility. The first longevity study in humans with low doses of DEP and BPAP was published in 2016. It indicated that the enhancer effect of these substances was responsible for their effect on the extension of life span. This book is primarily devoted to the analysis of the pharmacological profile of the two presently available, safe synthetic enhancers: DEP and BPAP. The information presented in it suggest that the enhancer-sensitive catecholaminergic and serotonergic neurons work in human and animal models similarly. The primary aim of its Author was to motivate clinicians to test whether synthetic enhancers can counteract brain aging in healthy humans similarly, as shown in a paper published in 2016 by Joseph Knoll and Ildiko Miklya (who wrote the Foreword to this book). Just about the time of completing this monograph and before its last chapter was posted on INHN’s website, Joseph Knoll passed away. Yet research in “enhancer-sensitive brain regulation has continued to develop drugs that would extend “longevity.”