AGE-RELATED-CHANGES IN SIGNAL-TRANSDUCTION - IMPLICATIONS FOR NEURONAL TRANSMISSION AND POTENTIAL FOR DRUG INTERVENTION

Problems associated with aging will become one of the leading health d ilemmas of the next century. Age-associated diseases, including those affecting the neuronal system, are increasing in frequency. Age-relate d deficiencies in the brain result in impaired motor functions, sleep, behaviour and cognitive functions. Good functioning of the brain is b ased on the communication between neurons, by means of signal sending and processing. Neuronal transmission is a very complex phenomenon whi ch involves neuromediator receptors, ion channels and various signal t ransduction systems. Aging is associated with modification of many bra in neurotransmitter and second messenger systems directly involved in signal transduction. Thus, signal transduction events that are deficie nt in the aged include calcium mobilisation, phosphatidylinositol brea kdown, cyclic nucleotides formation, accumulation of proto-oncogene tr anscripts and synthesis of new proteins, such as certain neurotransmit ters. Other events in signal transduction, such as protein tyrosine ki nase activity, G-protein structure and function and receptor-G-protein coupling, have not been studied in great detail as yet. Alterations i n these various intracellular signalling events may fundamentally infl uence the functional activity of neurons, and, in consequence, play an important role in the age-dependent alterations of brain functions. F uture studies are needed to better understand the molecular basis and the importance of signal transduction changes with aging. Such knowled ge will certainly lead to design of better drugs for the prevention or treatment of age-related deficiencies or diseases, such as Parkinson' s disease or Alzheimer's disease.