Conclusions and Proposals for Future Work – Parkinson's

Parkinson’s disease is a highly complex metabolic disease with many unknown contributing factors and mechanisms that result in the particular pathology. There are many aspects of the disease that need further investigation in order to better understand and treat the causes and effects of Parkinson’s.

One method I would propose to investigate would be to increase the amount of L-tyrosine and tyrosine hydroxylase by targeting and activating transcription factors for each. This would increase a precursor to dopamine as well as the enzyme that catabolizes the reaction of L-tyrosine to L-DOPA, thereby increasing the amount of L-DOPA that can be converted to dopamine. Experiments would need to be done to identify a way to activate the transcription factors and ensure that there are minimal or no adverse side effects to increasing the intracellular concentration of this molecule and enzyme.

A second area of further investigation would be to continue in the research looking for ways to regenerate neural cells. Until recently, it had been believed that brain cells could not be regenerated once lost, but a paper published in Cell in 2013 that was able to regenerate neurons in mice. This study layed the groundwork for applications in humans despite clear differences between mice and humans. The neural stem cells (NSCs) developed in this study should be studied further to find a way to implement them into humans. If possible, the dopaminergic cells that are being killed by Parkinson’s could be replaced continuously, thereby naturally aleviating the symptoms of the disease without medication. (Gage, Temple)

Diagram of Neuron Differentiation, google images
Diagram of Neuron Differentiation, google images

The third area I would investigate is the specific role the alpha-synuclein plays in the presynaptic neuron and whether or not modifications of the protein while maintaining the functionality could prevent aggregation. If alpha-synuclein were mutated in such a way that it was unable to oligomerize, the Lewy bodies wouldn’t form, thereby eliminating a main component of the pathology of the disease.

Alpha-synuclein protein, google images
Alpha-synuclein protein, google images

Overall, there is currently no way to prevent the disease nor pinpoint the exact cause of the disease. Until further research is conducted, the only option available to patients suffering from Parkinson’s disease is symptom management through one or many treatment options illustrated previously.

 

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History and Metabolic Context

Molecular Bases of the Disease State

Treatment and Disease Management