Parkinson’s disease….. A very tough disease to deal with. It seems the more you know about this disease the less you do actually know. Upon learning about PD I found myself asking more questions than I had to start. Lets see what you think…..
Parkinson’s Disease is a progressive disorder that affects the movement of person suffering with the disease. Around 1 million people in the United states suffer from Parkinson’s Disease and each year, around 60,000 new cases are diagnosed. The disease is characterized as a loss of dopamine neurotransmission in the human brain. This results in all of the symptoms characterized with PD such as, tremors, slowed movement, rigid muscles, impaired posture and balance, speech difficulties etc. These symptoms come at the cost of decreased dopamine neurotransmission that fuels the neurons and connections in your brain.
The current treatments for Parkinson’s disease are mainly to treat the symptoms of the disease. L-Dopa or levodopa is an amino acid that is a precursor to neurotransmitters dopamine, norepinephrine and epinephrine. It is able to cross the blood brain barrier and subsequently be converted into dopamine. Early studies showed that L-DOPA can cause sever side effects such as nausea and vomiting. These side effects were occurring because the L-DOPA was being converted into dopamine before it was crossing the blood brain barrier. So researchers added inhibitors of dopa-decarboxylase, which is the enzyme responsible for converted levodopa into dopamine; these inhibitors are called carbidopa and benserazide. L-DOPA medication provides relief to the tremors and shakiness symptoms of Parkinson’s disease. However, long-term use of the drug is shown to induce dyskinesia for 80% of patients that use levodopa. Dyskinesia is a disorder characterized by involuntary muscle movement. As patients progress with the treatment of levodopa the drug effects begin to wear off several hours of some or all doses of the medication. The reasons these motor fluctuations occur is unclear but is thought to be because of uneven changes in the basal ganglia circuitry resulting in the depletion of both dopamine and the drug treatment. Treatment of levodopa-induced dyskinesia is difficult but treatments used for the disease or dopamine agonists and neurosurgery. The main problems with both Parkinson’s disease and LID are the depletion of dopamine or the lack of dopamine circulating throughout the brain.
So what is the cause for this lack of dopamine Neurotransmission? Why do people get Parkinson’s Disease? Several factors point to genes. Specifically the SNCA gene which encodes for a-synuclein protein. A review article in the frontiers in molecular neuroscience journal discusses this very protein and why it is highly involved in Parkinson’s disease. In a general sense, a-synuclein is being turned on in a specific area on the protein called Serine 129 (S129) which is called hyperphosphorylation. This attributes to the formation of Lewy bodies which consequently, cause the cell to die and thus no dopamine present.
The article also goes into detail of different proteins that are related to the mechanism for the hyperphosphorylation of a-synuclein, such as polo-like kinase, casein kinases, and G protein coupled receptor kinase. However, more research needs to go into this mechanism in order to establish more of an understanding of this phenomenon. In addition to the hyperphosphorylation of a-synuclein, other factors such as the dysredulation of kinase proteins are attributed in the pathogenesis of PD. These kinases include proteins called LRRK2 and PINK1. Like the hyperphsophorylation of a-synuclein these are due to genetic factors and more research needs to be done.
Like I said, this disease is very complicated to understand. It seems like the more you know the less. Hoever, I reall think that this disease needs to be researched more and I believe eventually we can come up with an effective way to treat the causality of the disease not just the symptoms.
Treatments for the Cause or the Symptom?
