New Insights into Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder strongly associated with aging. Approximately 1% of the U.S. population is diagnosed with PD by the age of 65. It is characterized by resting tremors, bradykinesia, and rigidity that progressively worsens over time. Although the cause is unknown, symptoms of PD are linked to the degeneration and death of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc). Clinical application of L-DOPA, a dopamine precursor, is known to relieve the symptoms associated with PD. However, pathological studies are finding new insights into the causation of dopamine neural degeneration. This information can be used to develop preventive measures to reduce the incident of PD worldwide.

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According to “Calcium, Cellular Aging, and Selective Neuronal Vulnerability in Parkinson’s Disease,” mitochondrial oxidative stress is linked to apoptosis in SNpc. DA neurons in SNpc are pacemakers with long action potentials. Longer action potentials increase calcium entry along the dendrites of cells. Accumulation of calcium within a cell results in greater oxidative stress. Once inside, Ca²⁺ molecules directly or indirectly enter the mitochondria. Inside the mitochondria, Ca²⁺ molecules bind with oxygen to produce reactive oxygen species (ROS). ROS causes oxidative damage that results in the death of DA neurons. Isradipine, a calcium channel blocker, was used to reduce calcium entry at distal dendrites. As a result, the volume of mitochondria (mass) increased but the oxidative stress was reduced. Also, isradipine did not affect the pacemaking ability of DA neurons, making it an effective treatment to reduce apoptosis in SNpc.

http://www.nature.com/nrc/journal/v5/n11/fig_tab/nrc1738_F1.html

Additionally, “Microglial Activation and Dopamine Terminal Loss in Early Parkinson’s Disease” suggests that neuroinflammatory glial response is associated with degeneration of dopaminergic neurons in SNpc. Microglial cells repair neurons in the central nervous system (CNS). Therefore, activated microglial cells are important biomarkers for neuroinflammation. Post-mortem studies show widespread microglial activation in SNpc of animals with PD. Consequently, in this study, presynaptic dopamine transporter density was studied to investigate how microglial activity contributed to the degeneration of neurons. Results suggested that changes in microglial activation corresponded to dopaminergic terminal loss in PD brains.

With these new discoveries, we can understand the importance of early therapeutic interventions to prevent the progression of neural degeneration in PD. By nature, some individuals are more likely to develop PD due to genetic mutations and environmental factors. But, with the help of neuroprotective drugs, we can prevent degeneration of dopaminergic neurons to delay or eliminate the progression of Parkinson’s disease.

Works Cited

Ouchi, Yasuomi, Etsuji Yoshikawa, Yoshimoto Sekine, Masami Futatsubashi, Toshihiko Kanno, Tomomi Ogusu, and Tatsuo Torizuka. "Microglial Activation and Dopamine Terminal Loss in Early Parkinson's Disease." Annals of Neurology 57.2 (2005): 168-75. Web. 18 Oct. 2016. 

Stoessl, A. Jon, Stephane Lehericy, and Antonio P. Strafella. "Imaging Insights into Basal Ganglia Function, Parkinson's Disease, and Dystonia." The Lancet 384.9942 (2014): 532-44. Web. 18 Oct. 2016. 

Surmeier, D. James, Jaime N. Guzman, and Javier Sanchez-Padilla. "Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 19 Oct. 2016.