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Antioxidant treatment could halt neurodegeneration in early Parkinson’s

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Reprinted with the kind permission of Life Extension.

September 13 2017. An article appearing on September 7, 2017 in Science reports a potential benefit for antioxidant therapy against neurodegeneration in early Parkinson’s disease.

In human neurons derived from Parkinson’s disease patients, Dimitri Krainc and colleagues at Northwestern University identified a cascade that begins with mitochondrial oxidant stress leading to oxidized dopamine accumulation. This, in turn, results in a reduction in the activity of an enzyme known as lysosomal glucocerebrosidase, which weakens the function of the cells’ lysosomes:  organelles within the cell that contain over 60 different enzymes.  The cascade also results in the accumulation of alpha-synuclein, a protein that aggregates in the neurons of those with Parkinson’s disease. “The mitochondrial and lysosomal pathways are two critical pathways in disease development,” explained Dr Krainc, who is the the Aaron Montgomery Ward Professor and chair of neurology at Northwestern University Feinberg School of Medicine. “Combined with the alpha-synuclein accumulation, this study links the major pathological features of Parkinson’s disease.”

The researchers found that treatment with two different antioxidants, including N-acetylcysteine (NAC), interrupted the cascade. “One of the key strategies that worked in our experiments is to treat dopamine neurons early in the toxic cascade with specific antioxidants that improve mitochondrial oxidant stress and lower oxidized dopamine,” Dr Krainc stated. “With this approach, we found that we can attenuate or prevent the downstream toxic effects in human dopaminergic neurons.”

“Our long-term midbrain cultures demonstrated that early treatment with mitochondrial antioxidants reduced downstream accumulation of oxidized dopamine and alpha-synuclein, and rescued lysosomal dysfunction, highlighting the importance of early therapeutic intervention in the pathogenic cascade,” the authors conclude.

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