USP30

Proper degradation of dysfunctional mitochondria (mitophagy) is vital to prevent their accumulation and subsequent damaging effects. The ubiquitination process helps remove damaged and unwanted proteins, and defects in mitophagy play a large role in averting α-Syn toxicity, a pathological hallmark of PD. USP30 is a deubiquitinating enzyme (DUB) that directly removes ubiquitin tethered to the outer membranes of the mitochondria, and we believe inhibition of this enzyme might help protect against αSyn toxicity by enhancing mitophagy. Exciting preliminary data reveal that upregulation of mitophagy results in highly significant protection against αSyn toxicity in USP30 knock-out mice. By using the MTX012 compound to silence USP30, we will further our understanding of methods to restore mitophagy and increase neuroprotection with greater precision.