Targeting mitochondria for neuroprotection in Parkinson's disease

Several genetic causes of familial Parkinson's disease (PD) have now been identified and include mutations of genes encoding mitochondrial proteins. Mitochondrial complex I toxins can induce dopaminergic cell death and produce a parkinsonian state. Importantly, defects of mitochondrial function have been identified in postmortem substantia nigra from pathologically proven cases of PD.

These observations provide compelling evidence to support the notion that mitochondria play an important role in the pathogenesis of PD. Thus, targeting mitochondrial function to delay or prevent neuronal cell death would represent a logical means to modify the course of this disease. Several attempts have already been made in this respect, and have been tested in clinical trial.

To date, there is no unequivocal evidence for an effective intervention to slow the disease. However, several novel mitochondrial targets are now emerging, including the potential to manipulate the mitochondrial pool to maintain function via biogenesis and mitophagy.

This development in drug targets needs to be supported by a parallel improvement in clinical trial design to be able to detect a neuroprotective or disease-modifying effect over a reasonable time scale.