Current Adjustments to Parkinson’s Disease Treatment Methods

Parkinson’s Disease (PD) is a neurodegenerative disease whose symptoms circulate around a growing loss of motile control. The inability to move is attributed to a decline in dopamine as neurons decay, specifically in the substantia nigra (SNc). Previous research and treatments targeted dopamine. Currently, rather than preventing a decline in dopamine (DA) concentration, research has now been persuaded to address why dopaminergic neurons are dying in the first place.

http://www.medindia.net/patients/patientinfo/parkinsonsdisease.htm

Focus has been centered on combating oxidative stress and mitochondrial dysfunction- both of which correlate with calcium concentration. When intracellular calcium levels peak above normal, it signals for apoptosis- specifically, the calcium concentration in the mitochondria exceeds the amount needed to modulate energy production. Oxidative phosphorylation, part of the energy producing pathway, results in superoxides, free radicals, and reactive oxygen species that accumulate overtime suspending oxidative stress. This, alongside excess calcium, cause the mitochondria to swell and result in its dysfunction and eventually death.

Of the current literature, a paper published by Surmeier and colleagues at the Feinberg School of Medicine hypothesized that PD is the result of increased calcium entry which sustains oxidative stress and penetrates defenses typically in place to counter it. They indicated that dopaminergic neurons of the substantia nigra have a unique phenotype of pacemaking that may potentially render the cells vulnerable to continuous oxidative damage. The channels responsible for calcium entry are L-type with Cav 1.3 pore-forming subunits. These channels are not directly responsible for the pacemaking nature of the cell as pacemaking continues even after being antagonized by dihydropyridines (DHPs). However, the channels themselves are costly to the cell. The paper has indicated that PD prevention should seek to decrease calcium concentrations through L-type channel antagonists or Calcium channel antagonists (CCA). Of these are the previously mentioned DHPs that can cross the blood-brain barrier. The study is furthering research with Isradipine, a DHP with an affinity for the pore-forming subunit Cav 1.3.

http://www.thelancetnorway.com/journals/laneur/article/PIIS1474-4422(07)70246-6/fulltext

Other Parkinson’s treatment methods are emerging from this perspective. The Departments of Integrative Medicine, Neurology, and Radiology at Thomas Jefferson University have identified a natural molecule that is currently undergoing clinical trials. The molecule is n-acetylcysteine (NAC) which helps to overcome oxidative stress by revitalizing a natural antioxidant called glutathione. The study is observing basal ganglia dopamine transporter levels through imaging as well as comparing scores from Unified Parkinson’s Disease Rating Scale (UPDRS), a survey measuring progression of the disease.  

http://engineeredlifestyles.com/glutathione/natural-glutathione-supplements.html

The Lewis Katz School of Medicine at Temple University is more generally analyzing Mitochondrial channels involved with calcium. Recently, they have located a domain in mitochondrial Ca2+ uniporter (MCU) responsible for binding of calcium and magnesium. The hope is that further analysis of the structure will allow for the development of molecules that can mediate pathways dealing with the MCU and calcium flux.

References

Thomas Jefferson University. (2016, June 16). Natural molecule could improve Parkinson's. ScienceDaily. Retrieved October 18, 2016 from www.sciencedaily.com/releases/2016/06/160616141630.htm

Temple University Health System. (2016, August 25). Scientists discover structural clues to calcium regulation in cells: Insight into membrane gateway advances understanding of cardiovascular, neurological diseases involving mitochondrial dysfunction.ScienceDaily. Retrieved October 18, 2016 from www.sciencedaily.com/releases/2016/08/160825130031.htm

http://www.thelancetnorway.com/journals/laneur/article/PIIS1474-4422(07)70246-6/fulltext