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Calcium Channels Changes Could Point to New Therapies
- Jul 16 2013
Scientists have long proposed that imbalances in calcium underlie the brain changes that lead to Parkinson’s disease (PD). New research in the July issue of Brain identifies one specific calcium ion channel as a marker for Parkinson’s disease. This supports the idea that drugs already on the market, called calcium channel blockers, have potential to modify Parkinson’s disease progression.
Cells, including dopamine neurons lost to PD, are constantly working to balance calcium levels by pumping it in and out through channels. Too little calcium means the cell will not work properly and in PD, scientists propose that too much calcium can stress and kill dopamine neurons. More recently scientists hypothesized that a “triple hit” – too much calcium plus a build-up of alpha-synuclein protein and increased dopamine within the cells – can lead to cell death in PD. This theory was put forth by David Sulzer, Ph.D., from PDF’s Research Center at Columbia University Medical Center.
Researchers led by Michael J. Hurley, Ph.D., wanted to understand the role of calcium channels in PD – the doors of the cell that let calcium in and out. Do certain types of calcium channels make some neurons more susceptible to Parkinson’s disease? They studied brain tissue from nine individuals who died without any brain disease and 18 people who died with PD. The brain tissue had been generously donated after death, for research purposes, to a brain bank. The scientists used special staining techniques to map the location of the different kinds (subtypes) of calcium channels in several brain regions. They also looked for three different proteins that bind to, and detoxify, calcium ions within cells.
- Throughout the brains of people who had died with PD, calcium channel subtypes were distributed differently than in the brains of people without neurological disease.
- Changes in calcium ion channel distribution were evident in the brains of people who had died with early stage PD — even before neurons showed signs of PD damage.
- People who had died with PD had more calcium channels of one subtype, known as Cav1.3, throughout their brains. Researchers suspect increased use of this channel by neurons may make the cells susceptible to toxic calcium levels and more vulnerable to other damage and death.
What Does It Mean?
The link between cell death in PD and calcium metabolism continues to unfold. While calcium is crucial for the function of all the cells in our body, excess in calcium within the cells can lead to cell death. Because of the potential link between PD and calcium levels in neurons, this new study looked at the distribution of calcium ion channels in the human brain, and in the brains of people who died with PD.
The researchers hypothesized that calcium ion channels distribution is different in people with and without PD. Indeed, they found one specific type of channel that is more prevalent in brains of people with PD, even in areas not yet affected by the disease. The new study supports the investigation of blockers that target specifically the type of calcium channels over-represented in PD brains as therapies that might prevent the onset of PD or slow disease progression.
Indeed, drugs that block calcium channels commonly are used to treat high blood pressure, and epidemiological studies have suggested that people who take these therapies over a long period of time may be less likely to develop PD. One such drug, isradipine, which blocks other kinds of calcium channels better than it blocks the channel implicated in this study (Cav1.3), is currently being investigated in the US.
Reference: Hurley MJ, Brandon B, Gentleman SM, Dexter DT (2013) Parkinson's disease is associated with altered expression of CaV1 channels and calcium-binding proteins. Brain 136:2077–2097. DOI: 10.1093/brain/awt134 http://dx.doi.org/10.1093/brain/awt134
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Source Date: Jul 16 2013