Pre- and Postsynaptic Neurotoxic Effects of Dopamine Demonstrated by Intrastriatal Injection

Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine

“…In this and other related neurodegenerative diseases, the catecholamines themselves are hypothesized to play a role as endogenous neurotoxins (Graham, 1978;Stokes et al, 1999). Such a role is suggested by the well established neurotoxicity of 6-hydroxydopamine and is supported by experimental evidence in vitro of catecholamine-induced toxicity in cell culture systems Rosenberg, 1988;Michel and Hefti, 1990;Masserano et al, 1996;Shinkai et al, 1997;Velez-Pardo et al, 1997), and in vivo, after intrastriatal injections of dopamine in rats (Filloux and Townsend, 1993;Hastings et al, 1996b).…”

Oligomerization and Membrane-binding Properties of Covalent Adducts Formed by the Interaction of α-Synuclein with the Toxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde (DOPAL)

“…This hypothesis is corroborated by the fact that the neurotoxicity associated with aS overexpression is remarkably reduced when DA synthesis is inhibited (7), and the toxicity of oxidized catechol metabolites is exacerbated by the expression of WT aS or the PD-linked A53T variant (8). The fact that DA itself, at concentrations found in dopaminergic neurons, is not able to impair neuron functionality and cause cell death as found in PD (9) suggests that another molecule produced via DA metabolism could be responsible for this selective neuronal degeneration (10).…”

Insecticide Exposure in Parkinsonism

“…We have previously speculated that enhanced turnover of dopamine may itself be neurotoxic, because the metabolism and auto-oxidation of dopamine generates cellular oxidative stress (Dawson et al, 1995) and high levels of dopamine in the brain can be neurotoxic (Filloux and Townsend, 1993). However, we would expect that cell toxicity would be reflected in a loss of striatal dopamine, but this effect was not observed, perhaps due to the short duration of exposure (two weeks).…”