L-type Ca2+ channel blockers for neuroprotection in Parkinson’s Disease?

Loss of dopamine neurons in the substantia nigra produces motor symptoms characteristic of Parkinson’s disease. Mitochondrial oxidative stress is widely viewed as being responsible for this loss, but why these specific neurons should be stressed is a mystery. Guzman and colleagues have found that the normal pacemaking activity of these dopamine neurons creates mitochondrial oxidative stress. Loss of the DJ-1 protein, which has been associated with early-onset Parkinson’s disease, exacerbates this oxidative stress in substantia nigra dopamine neurons. By elevating mitochondrial oxidative stress, calcium entry into these cells during normal pacemaker activity makes substantia nigra dopamine neurons more vulnerable to toxins and could accelerate loss with age. Drugs approved for human use to antagonize calcium entry through L-type channels are proposed to be potentially neuroprotective in Parkinson’s disease.

Guzman JN et al.: Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 468: 696-700 (2010).

http://www.ncbi.nlm.nih.gov/pubmed/21068725