L-α-Aminoadipic Acid is a lysine metabolite with neuroexcitatory properties, which competitively inhibits glutamate transporters with a Ki value of 192µM[1,2]. L-α-Aminoadipic Acid is one of the isomeric forms of 2-Aminoadipic acid and is crucial for neurotransmitter regulation and glutamate transport inhibition[3]. L-α-Aminoadipic Acid is commonly used in research to selectively inhibit astrocyte function for investigating their physiological and pathological roles, and also serves as a precursor for β-lactam antibiotics in the development of novel antibiotics[4,5].
In vitro, treatment of mouse cerebellar cells with L-α-Aminoadipic Acid (0.34mM) for 2h induced reversible swelling in approximately 80% of astrocytes; prolonged treatment for 40h resulted in the death of 97% of astrocytes[6]. In rat amygdala slices, treatment with L-α-Aminoadipic Acid (1mM) for ≥90min increased the nuclear area of glial fibrillary acidic protein (GFAP)-positive astrocytes and significantly reduced the N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) evoked by strong stimulation in the thalamo-LA pathway[7].
In vivo, intravitreal injection of L-α-Aminoadipic Acid (8µM/eye; 50µL) in carp led to a reduction in S-potentials and a relatively lower resting potential in retinal horizontal cells within 2-4h; the voltage characteristics of horizontal cells returned to normal within 1-2 days[8]. In adult male Wistar rats, bilateral microinjection of L-α-Aminoadipic Acid (25µg/µL/day; 1µL/rat (0.5µL per side)) into the hippocampal CA1 region for 3 days significantly reduced the number of GFAP-immunoreactive (GFAP-ir) astrocytes in the hippocampus, resulting in impaired passive avoidance memory and increased anxiety-like behavior[9].
References:
[1] WU H Q, UNGERSTEDT U, SCHWARCZ R. l-α-Aminoadipic acid as a regulator of kynurenic acid production in the hippocampus: a microdialysis study in freely moving rats[J]. European journal of pharmacology, 1995, 281(1): 55-61.
[2] MCBEAN G J. Inhibition of the glutamate transporter and glial enzymes in rat striatum by the gliotoxin, alpha aminoadipate[J]. British journal of pharmacology, 1994, 113(2): 536.
[3] SHI W, YANG Z, FU P, et al. Metabolite 2-aminoadipic acid: implications for metabolic disorders and therapeutic opportunities[J]. Frontiers in Pharmacology, 2025, 16: 1569020.
[4] ISOBE K, TOKUTA K, NARITA Y, et al. Production of Nα-benzyloxycarbonyl-L-aminoadipic acid and Nα-benzyloxycarbonyl-D-aminoadipic acid with Rhodococcus sp. AIU Z-35-1[J]. Journal of Molecular Catalysis B: Enzymatic, 2004, 32(1/2): 27-32.
[5] GUIDETTI P, SCHWARCZ R. Determination of α-aminoadipic acid in brain, peripheral tissues, and body fluids using GC/MS with negative chemical ionization[J]. Molecular brain research, 2003, 118(1/2): 132-139.
[6] HUCK S, GRASS F, HATTEN M E. Gliotoxic effects of α-aminoadipic acid on monolayer cultures of dissociated postnatal mouse cerebellum[J]. Neuroscience, 1984, 12(3): 783-791.
[7] LI Y, SACCHI S, POLLEGIONI L, et al. Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level[J]. Nature communications, 2013, 4(1): 1760.
[8] SUGAWARA K, TORIGOE K, OKOYAMA S, et al. Neurotoxic effects of l-α-aminoadipic acid on the carp retina: a long term observation[J]. Neuroscience, 1990, 36(1): 155-163.
[9] JAHANSHAHI M, ELYASI L, NIKMAHZAR E. L-α-aminoadipic Acid-Induced Astrocytes Inhibition in the Hippocampal CA1 Region Leads to Anxiety-like Behavior and Memory Impairment[J]. Basic and Clinical Neuroscience, 2025, 16(1).
L-α-Aminoadipic Acid是一种具有神经兴奋特性的赖氨酸代谢物，可竞争性抑制谷氨酸转运蛋白，Ki值为192μM[1,2]。L-α-Aminoadipic Acid是2-Aminoadipic acid的其中一种异构体形式，对神经递质调节和谷氨酸转运抑制至关重要[3]。L-α-Aminoadipic Acid通常用于靶向抑制星形胶质细胞功能以探究其生理与病理作用的研究，也作为β-内酰胺类抗生素的前体用于新型抗生素的开发[4,5]。
在体外，L-α-Aminoadipic Acid（0.34mM）处理小鼠小脑细胞2h，引起约80%的星形胶质细胞出现可逆性肿胀；若持续处理40h，则导致97%的星形胶质细胞死亡[6]。L-α-Aminoadipic Acid（1mM）处理大鼠杏仁核切片≥90min，引起神经胶质纤维酸性蛋白（GFAP）阳性的星形胶质细胞核面积增大，并显著降低了由强刺激诱发的thalamo-LA通路中N-甲基-D-天门冬氨酸受体（NMDAR）介导的兴奋性突触后电流（EPSC）[7]。
在体内，L-α-Aminoadipic Acid（8μM/eye; 50μL）通过眼内注射处理鲤鱼，2-4h后视网膜水平细胞的S电位降低且静息电位相对较低，1-2天后水平细胞的电压特征恢复正常[8]。L-α-Aminoadipic Acid（25μg/μL/day; 1μL/rat (0.5μL on each side)）通过双侧海马CA1区微量注射处理成年雄性Wistar大鼠3天，显著降低了海马体中GFAP-immunoreactive（GFAP-ir）星形胶质细胞的数量，并导致被动回避记忆受损和焦虑样行为增加[9]。