The Melanotropic Peptides [antikvár]

PrefaceJAN N. JOHANNESSENDivision of Toxicological Research FDA/CFSAN 8301 Muirkirk Road Laurel, Maryland 20708andM. ANTHONY VERITYDivision of Neuropathology and Brain Research Institute UCLA Medical Center Los Angeles, California 90024-1732During the last decade, numerous studies have identified cellular mechanisms which participate in the initiation and physiological transduction of signaling mechanisms within the central nervous system. A major result of these studies is the recognition that these same pathways, activated abusively, may be transformed into weapons of neuronal destruction. A number of insults are associated with the induction of abnormal cellular processes, resulting in neuronal injury and loss. These include stroke (ischemia), chronic alcoholism, drugs of abuse (amphetamines, "ecstasy"), environmental toxins (e.g. heavy metals), food toxins (excitatory amino acids, e.g. domoic acid), idiopathic neurodegenerative disease (Parkinson's, Alzheimer's), trauma, and CNS infection.Biochemical markers used to ascertain the degree of neuronal damage or loss have been those most commonly associated with specific neuronal phenotypes, such as neurotransmitters or their synthetic enzymes and receptors. While these approaches are sensitive, they are highly selective for specific cell types. Furthermore, since loss of a particular transmitter, receptor or enzyme is usually indicative of neuronal loss, these measures do not further our understanding of the degenerative process, but only indicate the magnitude.Anatomical markers are often useful because specific morphological changes associated with degenerating neurons, including reactive changes in non-neuronal elements, can be visualized. Clearly these morphological changes seen with traditional histological techniques have biochemical correlates. The emphasis of this conference has been on identifying some of the biochemical events which occur during the process of neuronal degeneration rather than those which signal the end result of that process. Furthermore, models of neuronal injury from a wide variety of causes have been included in hopes that certain biochemical events common to injury will emerge.The expanding list of biomarkers associated with neuronal injury and degeneration should lead to a number of practical benefits. Pursuing the functional roles of these markers in the degenerative process will lead to a more complete understanding of the causes and progression of neuronal injury, point to novel ameliorative strategies. One current research emphasis in the treatment of neurodegenerative diseases such as parkinsonism, has been on reversal of the disease by neuronal transplant. A more conservative approach is the slowing or halting of the degenerative process by early pharmacological intervention. The success of this strategy will ultimately depend on the ability to detect the earliest stages of the disease. Hence, there is an undisputed need for accurate and sensitive markers of the degenerative process which have predictive diagnostic value.