Experimental Biology 2010: Dopamine Degradation By Hypochlorous Acid: Implications For Parkinsonism

Purpose of Study: Hypochlorous acid (HOCl) is formed in the brains of Alzheimer Disease patients (Yap et al. (2007) Cellular Signalling 19: 219) and 30% of these individuals develop parkinsonism. The latter condition implies a loss of dopamine. This loss may be due to reaction of HOCl with dopamine to form chlorodopamine. Dopamine is derived from tyrosine, which reacts with HOCl to from 3-chlorotyrosine. These observations suggest the hypothesis that parkinsonism in Alzheimer Disease may be due to the loss of dopamine reacting with HOCl to form chlorodopamine.

Methods Used: As an initial test of this hypothesis, HOCl was reacted with dopamine and the products analyzed by spectrophotometry.

Summary of Results: The chlorination of dopamine resulted in immediate increases in the absorbance at the amine (~205-230 nm) and phenol (~280 nm) regions, as well as, the formation of new product at 460 nm. Addition of HOCl scavengers, including hydrogen sulfide and taurine, blocked the chlorination of dopamine. The content of these scavengers in brain decreases with age and suggests another mechanism by which chlorodopamine formation might be accentuated in Alzheimer Disease. The early reaction products of dopamine and HOCl were also toxic to cultured SH SY5Y cells.

Conclusions: Taken together these observations suggest that the HOCl formed during Alzheimer Disease may chlorinate dopamine and contribute to the parkinsonism exhibited by a portion of these patients.