An answer to "The Nagging Question of the Function of N-Acetylaspartylglutamate"

Abstract

Abstract In 1997, a paper was published entitled Nagging Question of the Function of N-Acetylaspartylglutamate. N-acetylaspartylglutamate (NAAG) is an unusual acetylated dipeptide that is synthesized by neurons, but whose complete metabolism requires four different enzymes and a specific receptor distributed among three different cell types in the brain. In 2007, it was hypothesized that the primary function of NAAG was that of a homeostatic neuronal-astrocyte-vascular system control mechanism. The purpose of this mechanism being to initiate focal hyperemic responses increasing the availability of oxygen and glucose to stimulated neurons in order to replenish their energy stores and thus maintain their ability to transmit a full range of meaningful frequency-encoded messages. In this communication, evidence is presented supporting the NAAG feedback control hypothesis. This evidence shows that NAAG is not required by individual neurons for survival, for myelination, or for their basic spiking activity by which signals are transmitted at synapses. However, in the absence of NAAG, or if its complex intercellular metabolism is compromised, higher brain cognitive functions and coordinated motor activities that are dependent on the integrity of frequency-encoded signals are negatively affected.