caa a22 4500 46788174X CHVBK 20180406152722.0 cr unu---uuuuu 170328e20061101xx s 000 0 eng 10.1007/s00702-006-0591-6 doi (NATIONALLICENCE)springer-10.1007/s00702-006-0591-6 From benefit to damage. Glutamate and advanced glycation end products in Alzheimer brain [Elektronische Daten] [P. Riederer, S. Hoyer] Summary.: The glutamatergic system is the most widespread neurotransmitter system in the mammalian brain. It is connected to the acetylcholinergic neurotransmitter system to form the glutamatergic/aspartatergic-acetylcholinergic circuit, which is the morphobiochemical basis of learning, memory and cognition assisted by the glutamatergic N-methyl-D-aspartate receptor, which mediates long-term potentation as the fundamental molecular mechanisms of these mental capacities. Glutamate and acetylcholine as ligands of the two neurotransmitter systems are products of the neuronal glucose metabolism as holds true also for advanced glycation end products (AGEs), which are markers of damaged and/or aged proteins. During normal aging, both the neurotransmitters glutamate and acetylcholine undergo strong functional variations. Their synthesis was found to be reduced as a common feature. In contrast, basal release of acetylcholine and receptor number decrease, whereas basal release of glutamate and receptor number increase. AGEs increase during aging obviously preferentially in glutamatergic pyramidal neurons in cerebral cortical layers prone to neurodegeneration. In sporadic Alzheimer disease (SAD), glutamate concentration was shown to fall since it may serve as a substitute for lacking glucose in the beginning of the disease. In contrast, glutamate receptor density was found to be much less involved indicating an excessive activation of the glutamatergic neurotransmitter system particularly via the NMDA receptor, mediating endogenous excitotoxicity. The morphological hallmarks of SAD neuritic plaques and neurofibrillary tangles have been demonstrated to crosslink with AGEs causing an increased rate of free radical production. First data from animal studies and investigations on human beings may indicate that the NMDA receptor antagonist memantine may have beneficial effects on the course of SAD and its clinical symptoms. Springer-Verlag, 2006 Keywords: Alzheimer disease, brain, glutamate, NMDA-receptor, advanced glycation end products, cell damage, memantine nationallicence Riederer P. Institute of Clinical Neurochemistry and National Parkinson Foundation Centre of Excellence Laboratory, Clinic for Psychiatry and Psychotherapy, Bayerische Julius-Maximilians-University of Würzburg, Würzburg, Germany aut Hoyer S. Institute of Pathology, University of Heidelberg, Heidelberg, Germany aut Journal of Neural Transmission Springer-Verlag 113/11(2006-11-01), 1671-1677 0300-9564 113:11<1671 2006 113 702 https://doi.org/10.1007/s00702-006-0591-6 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-006-0591-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Riederer P. Institute of Clinical Neurochemistry and National Parkinson Foundation Centre of Excellence Laboratory, Clinic for Psychiatry and Psychotherapy, Bayerische Julius-Maximilians-University of Würzburg, Würzburg, Germany aut NATIONALLICENCE 700 1- Hoyer S. Institute of Pathology, University of Heidelberg, Heidelberg, Germany aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer-Verlag 113/11(2006-11-01), 1671-1677 0300-9564 113:11<1671 2006 113 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer