Tareq Hanna

Dopathiazines Magnify Mn-dependent Oxidative Stress in Manganism

Authors: Tareq Hanna (biological sciences), 2021 Winner ðŸ†, Dr. David Njus and Praneet Marwah

Faculty mentor: David Njus

Abstract

Manganism is a condition caused by chronic high levels of Manganese. Interestingly, this selectively disrupts signaling in the basal ganglia, so Manganism is a movement disorder resembling Parkinson's Disease. The basal ganglia are a dopamine-rich region of the brain, and we have discovered that MnCl2 speeds up the redox cycling of dopamine-derived benzothiazines, called dopathiazines. This redox cycling reduces O2 to superoxide and hydrogen peroxide, so it leads to oxidative stress. This effect is only seen with Mn and is not reproduced by other metal ions such as Fe, Cu, Zn, Co, Ca or Mg. The Mn effect requires that inorganic phosphate be present, suggesting that the phosphate is involved in stabilizing a Mn:dopathiazine complex. It is proposed that these or similar endogenous dopamine derivatives may magnify Mn-dependent oxidative stress accounting for the neurological selectivity of manganism.

Poster pitch

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