Destruction of catecholamine-containing neurons by 6-hydroxydopa, an endogenous amine oxidase cofactor
- Cite this article as:
- Kostrzewa, R.M. & Brus, R. Amino Acids (1998) 14: 175. doi:10.1007/BF01345259
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The amino acid, 6-hydroxydopa (6-OHDOPA), found at the active site of amine oxidases, exists as a keto-enol. Exogenously administered 6-OHDOPA is an excitotoxin likeβ-N-oxalylamino-L-alanine (BOAA) andβ-N-methylamino-L-alanine (BMAA), acting at the non-N-methyl-D-aspartate (non-NMDA)α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. BMAA and BOAA are causal factors of neurolathyrism in humans. Much exogenously administered 6-OHDOPA is biotransformed by aminoacid decarboxylase (AADC) to the highly potent and catecholamine (CA) selective neurotoxin, 6-hydroxydopamine (6-OHDA). 6-OHDOPA destroys locus coeruleus noradrenergic perikarya and produces associated denervation of brain by norepinephrine-(NE) containing fibers. Opiopeptides and opioids enhance neurotoxic effects of 6-OHDOPA on noradrenergic nerves, by a naloxone-reversible process. An understanding of mechanisms underlying neurotoxic effects of 6-OHDOPA can be helpful in defining actions of known and newfound amino acids and for investigating their potential neurotoxic properties.
Keywords6-Hydroxydopa6-HydroxydopamineNoradrenergic neuronsNeurotoxicityExcitatory amino acids
excitatory amino acid
standard error of the mean