Potential role of N-methyl-D-aspartate receptors as executors of neurodegeneration resulting from diverse insults: focus on memantine.
Glutamatergic neurotransmission is critical to normal learning and memory and when the activity of glutamate neurons becomes excessive, or the normal function of its primary receptors becomes dysfunctional, this may lead to pathological changes associated with age-related neurodegenerative diseases. Anomalous glutamatergic activity associated with Alzheimer's disease may be due to a postsynaptic receptor and downstream defects that produce inappropriately timed or sustained glutamate activation of N-methyl-D-aspartate receptors, leading to neuronal injury and death and cognitive deficits associated with dementia. The mechanisms leading to the condition of chronically depolarized membranes on vulnerable neurons in the Alzheimer's disease brain are likely due to a complex interaction between oxidative stress, mitochondrial failure, chronic brain inflammation and the presence of amyloid-beta and hyperphosphorylated-tau; each of these factors are highly interrelated with each other and are discussed with an emphasis upon potential therapeutic mechanisms underlying the neuroprotective actions of memantine.
Wenk
Gary L
GL
Department Psychology & Neuroscience, Ohio State University, Ohio, USA.
Parsons
Chris G
CG
Danysz
Wojciech
W
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008559:Memantine / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008559:Memantine