NYMC Faculty Publications
Inflaming the Diseased Brain: A Role for Tainted Melanins
Author Type(s)
Faculty
DOI
10.1016/j.bbadis.2015.01.004
Journal Title
Biochimica Et Biophysica Acta
First Page
937
Last Page
50
Document Type
Article
Publication Date
5-1-2015
Abstract
Inflammation plays a crucial role in neurodegenerative diseases, but the irritants responsible for this response remain largely unknown. This report addressed the hypothesis that hypochlorous acid reacts with dopamine to produce melanic precipitates that promote cerebral inflammation. Spectrophotometric studies demonstrated that nM amounts of HOCl and dopamine react within seconds. A second-order rate constant for the reaction of HOCl and dopamine of 2.5 × 10(4)M(-1)s(-1) was obtained by measuring loss of dopaminergic fluorescence due to HOCl. Gravimetric measurements, electron microscopy, elemental analysis, and a novel use of flow cytometry confirmed that the major product of this reaction is a precipitate with an average diameter of 1.5 μm. Flow cytometry was also used to demonstrate the preferential reaction of HOCl with dopamine rather than albumin. Engulfment of the chlorodopamine particulates by phagocytes in vitro caused these cells to release TNFα and die. Intrastriatal administration of 10(6) particles also increased the content of TNFα in the brain and led to a 50% loss of the dopaminergic neurons in the nigra. These studies indicate that HOCl and dopamine react quickly and preferentially with each other to produce particles that promote inflammation and neuronal death in the brain.
Recommended Citation
Jeitner, T. M., Kalogiannis, M., Patrick, P. A., Gomolin, I., Palaia, T., Ragolia, L., Brand, D., & Delikatny, E. J. (2015). Inflaming the Diseased Brain: A Role for Tainted Melanins. Biochimica Et Biophysica Acta, 1852 (5), 937-50. https://doi.org/10.1016/j.bbadis.2015.01.004
