Breakthrough in pinpointing the biochemistry of Parkinson's brain injuryRSS Feed
Scientists from Purdue University in Indianapolis have identified a protein mutation that leads to the brain injury characteristic of Parkinson's disease.
The study, which is reported on Purdue University's news website, used quantitative mass spectrometry techniques to monitor the effects of normal and mutated forms of the protein DJ-1, which is known to play a potent neuroprotective role. When a subtle mutation results in the "switching off" of the protein, it becomes incapable of protecting neurons from "Lewy bodies" - clumps of unfolded protein that cause cell death and brain injury.
For Parkinson's sufferers, the destruction occurs in a brain structure known as the substantia nigra, and the familiar symptoms of poor balance, muscular rigidity, tremor and impaired movement appear as a result. The Purdue team identified a precise biochemical mechanism caused by the mutation: it prevents DJ-1 from facilitating a crucial, neuroprotective chemical reaction on another protein, alpha-synuclein. When this reaction fails, alpha-synuclein molecules unfold and become "sticky," clumping together with other proteins into aggregates that cause cell death.
Co-author Dr Jean-Christophe Rochet, Associate Professor of Medicinal Chemistry and Molecular Pharmacology at Purdue, said that current methods of treatment were similar to hormone replacement therapies in as much as they were designed to add back what the lost cells actually used to produce.
He added: "Understanding this error in a key protein could help researchers find a way to prevent cell death in the first place. Perhaps a compound could be found that could correct the problem and resurrect the protective function of the protein. Of course interventions would be needed in many places to treat the disease, but this could be one of several places to target for a potential treatment."
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