Parkinson’s disease (PD) is a very tough disease to discuss because of its progressive nature and how debilitating it can be. To any of you who knows someone that has PD you know exactly what I am talking about. It starts out as barely noticeable tremors, stiffness, and moving slower. Now the stiffness and slowing of movement can also be attributed to old age and that is what makes this disease so difficult to diagnose. One other noticeable sign that only presents in Parkinson’s is the arms remaining stationary while an individual walks and also the inability to turn while walking without considerable time and effort.
In the United States there are about 1 million people that are diagnosed with the disease and around the world there are approximately 4 million people. Every year there is about 60,000 people diagnosed with the disease in the United States alone. Most PD onset is at the age of 60 or older, but as with many neurodegenerative diseases there is a small amount of early onset conditions. This usually accounts for only 5-10% of all cases.
Parkinson’s disease is defined by an early selective loss of dopamine producing neurons in the substantia nigra and by the formation of Lewy bodies. These Lewy bodies are an accumulation of alpha-synuclein and other misfolded proteins that cause oxidative stress and have other toxic effects that can eventually lead to dopamine neuron death. Hence, the loss of some of some movements and the tremors that are commonly associated with the disease. The reason alpha-synuclein aggregates in PD is due to it being phosphorylated by kinases that are dysfunctional. In the normal human brain alpha-synuclein is phosphorylated only about 4% of the time, but in diseased brains this number can be upwards of 90%. This causes the misfolded alpha-synuclein to aggregate and act like prions. This simply means that the misfolded alpha-synuclein can bump into normal alpha-synuclein and cause that alpha-synuclein to become misfolded as well. This leads to a continuous cascade of Lewy Body formation, which in turn leads to loss of dopamine producing neurons.
Now the classical treatment for Parkinson’s is L-Dopa. The idea behind this drug is that there is simply a lack of dopamine in the brain so dopamine needs to be added to offset the loss of dopamine. The main reason why dopamine is not given as a treatment is that it cannot cross the Blood Brain Barrier (BBB). This is the barrier that prevents viruses, bacteria, and other molecules from entering the brain and causing problems. However, the solution to this is giving L-Dopa that is an amino acid precursor as a treatment. This molecule can cross the BBB and can be converted to dopamine once inside the brain. The treatment of L-Dopa can alleviate the tremors and shakiness of Parkinson’s and also improve the ability to walk normally. However, prolonged use of L-Dopa can lead to dyskinesia, which means involuntary muscle movement.
Parkinson’s disease is a progressive disease that eventually can lead to debilitating tremors, stiffness, and slow movement. Like many other neurodegenerative diseases there is no cure. However, L-Dopa can alleviate many of the symptoms and improve the quality of life of those diagnosed with the disease. More research needs to be done to ensure that a cure is developed to stop this disease in its tracks.
Parkinson’s Disease: What Is L-Dopa and How Does It Act?
