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Pathogenesis of PD in alpha-synuclein cleavage by matrix metalloproteinase-3

A recent finding from our research strongly indicates that matrix metalloproteinase-3 (MMP-3), a protein-cleaving enzyme, plays a pivotal role in degeneration of dopamine neurons in models of Parkinson's disease, and that modulation of MMP-3 may prevent dopamine neuronal degeneration in PD. We will undertake further investigation into MMP-3 and alpha-synuclein toxicity in dopamine neurons and the effects of several candidate compounds that inhibit MMP-3 activity on dopamine neuronal degeneration. Our hope is that our investigation may elucidate a novel therapeutic approach to PD.

Final Outcome

Dr. Joh tested the role of MMP-3, a protease, for its ability to cleave alpha-synuclein into potentially toxic fragments. Interestingly, mice deficient for MMP-3 appeared resistant to MPTP-induced dopamine neuron degeneration, an effect mimicked by MMP-3 inhibitors. Dr. Joh is continuing to explore the potential of MMP-3 to cleave other proteins implicated in PD.

Results of this work were published in the journals Neurotoxicity Research and the Journal of Neurochemistry.


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