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. 2022 Feb 8;17(9):1861–1866. doi: 10.4103/1673-5374.335690

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Copyright: © Neural Regeneration Research

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Astrocyte protects dopaminergic neurons against aminochrome neurotoxicity.

Astrocytes take up dopamine after neurotransmission through dopamine transporter (DAT), organic cation transporter-3 (OCT3) and plasma membrane transporter (PMAT) into cytosol where dopamine autoxidizes at physiological pH to DAoQ. DAoQ is very unstable and instantly cyclizes to AM at rate of 0.15 s^–1. AM induces an increase in mRNA expression of GSTM2 and exosomes mediate intercellular transport GSTM2 from astrocytes into dopamine neurons. GSTM2 conjugates DAoQ with GSH to 5-glutathionyldopamine that is degraded to 5-cysteinyldopamine, which will be deposited in the neuromelanin or be excreted into cerebrospinal fluid. GSTM2 also catalyze GSH conjugation of AM to 4-S-glutathionyl-5,6-dihydroxyindoline, which it is not able to oxidize in the presence of dioxygen, hydrogen peroxide and superoxide, and it is unable to participate in neurotoxic redox cycling reactions. Unpublished data. AM: Aminochrome; DAoQ: dopamine o-quinone; GSH: glutathione; GSTM2: glutathione transferase M2-2.