β--methylamino--alanine (BMAA) has been shown to inhibit vesicular monoamine transporter 2 (VMAT2), thereby preventing the uptake of monoaminergic neurotransmitters into platelet dense granules and synaptic vesicles. The inhibition is hypothesized to be through direct association of BMAA with hydroxyl groupꟷcontaining amino acid residues in VMAT2. This study evaluated whether BMAA-induced inhibition of VMAT2 could be prevented directly by co-incubation of BMAA with amino acids, and if this protection was specific for BMAA inhibition of VMAT2. -tyrosine, and to a lesser extent -serine, was able to prevent BMAA-induced VMAT2 inhibition in a concentration-dependent manner, whereas neither -threonine nor amino acids without side chain hydroxyl groups could reduce this inhibition. Reserpine-induced VMAT2 inhibition was unaffected by any of the amino acids. These data support the hypothesized interaction between BMAA and hydroxyl groupꟷcontaining amino acids and suggests that this interaction might be leveraged to protect against the toxicity of BMAA.

中文翻译：

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含羟基蛋白氨基酸对 β-N-甲氨基-L-丙氨酸引起的囊泡单胺转运蛋白 2 抑制的保护作用

β-甲氨基-丙氨酸 (BMAA) 已被证明可以抑制囊泡单胺转运蛋白 2 (VMAT2)，从而阻止单胺能神经递质被血小板致密颗粒和突触小泡摄取。推测这种抑制是通过 BMAA 与 VMAT2 中含有羟基的氨基酸残基直接结合而实现的。本研究评估了是否可以通过 BMAA 与氨基酸共孵育来直接防止 BMAA 诱导的 VMAT2 抑制，以及这种保护是否对 BMAA 对 VMAT2 的抑制具有特异性。 -酪氨酸以及较小程度的-丝氨酸能够以浓度依赖性方式阻止BMAA诱导的VMAT2抑制，而-苏氨酸和没有侧链羟基的氨基酸都不能减少这种抑制。利血平诱导的 VMAT2 抑制不受任何氨基酸的影响。这些数据支持了 BMAA 和含羟基氨基酸之间假设的相互作用，并表明这种相互作用可以用来防止 BMAA 的毒性。