N-acetylaspartylglutamic acid (NAAG)

N-acetylaspartylglutamic acid (NAAG) is an endogenous neuropeptide present in high concentrations within the brain. It is released from neurons upon depolarization through a calcium-dependent process. Functionally, NAAG acts as an agonist at the metabotropic glutamate receptor 3 (mGluR3), where it inhibits cyclic AMP production in both neurons and astrocytes. It also serves as an antagonist at NMDA receptors. After release, it is primarily catabolized by glutamate carboxypeptidase II on astrocyte surfaces into N-acetylaspartate and glutamate. NAAG has been studied for its role in modulating neurotransmission and synaptic plasticity. Its levels and metabolism are altered regionally in several neuropsychiatric disorders such as Huntington’s disease and Alzheimer’s disease. In clinical settings outside the CNS, topical formulations of NAAG have demonstrated anti-inflammatory effects—specifically as a mast cell stabilizer with C3 convertase antagonist activity—in conditions like allergic conjunctivitis. Despite these biological activities and therapeutic explorations related to its modulation or breakdown inhibition (e.g., with peptidase inhibitors), **NAAG itself is not a classical drug target** such as a receptor or enzyme but rather an endogenous ligand/neuropeptide that acts on other targets like mGluR3 or NMDA receptors. > "Spaglumic Acid (N-Acetylaspartylglutamate; NAAG) is released upon depolarization by a Ca2+-dependent process and is an agonist at mGluR3 receptors and an antagonist at NMDA receptors... The levels of Spaglumic Acid [NAAG]... are altered...in several neuropsychiatric disorders"[1]. > "Following synaptic release, α‐NAAG activates postsynaptic metabotropic glutamate receptor 3 (mGluR3) to inhibit cAMP production..."[7]. **Note:** The query refers to “Anti-inflammatory effect via N-acetylaspartylglutamic acid” as if this were itself a molecular target/receptor; however, **N-acetylaspartylglutamic acid/NAAG is not a molecular target but rather an endogenous peptide ligand** that exerts anti-inflammatory effects through action on other targets such as mGluR3. Therefore, *is_incorrect* = true — this entry does not correspond to a canonical therapeutic target but rather describes the mechanism by which this molecule exerts effects via actual protein targets. If you need structured information about the actual protein targets involved—such as “Metabotropic glutamate receptor 3” or “NMDA receptor”—please specify which one you would like detailed next.

Other names

Spaglumic acidα-Spaglumic AcidN-acetyl-L-aspartyl-L-glutamateAc-Asp-Glu(3-)

Agonist at metabotropic glutamate receptor 3 (mGluR3), leading to inhibition of cAMP production in neurons and astrocytes; Antagonist at NMDA receptors