Review Volume 13, Issue 7 pp 10770—10795

Alzheimer’s disease as a chronic maladaptive polyamine stress response

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Figure 3. A hypothetical synapse diagram. Arginine decarboxylase (ADC) converts arginine into agmatine and carbon dioxide. Agmatine is a neurotransmitter that is synthesized, stored in vesicles, and released following depolarization. Agmatine binds with high affinity to α2-adrenoceptors (α2) and imidazoline receptors (IR). It antagonizes glutamatergic NMDA, AMPA, and nACh receptors. Polyamines, spermine, and spermidine modulate the activation of NMDA receptors via a unique allosteric regulatory site at the extracellular domain. The pore of ionotropic glutamate receptors is easily accessible to cationic polyamines, which are capable of blocking the ions movement via the channels. Polyamines efficiently block ACh-induced currents via nAChR.