A friend of mine is quite fond of tattoos. She has several, and they all have their own special meaning. My favorite of hers, though, is the words “I love you” in her dad’s handwriting. This kind of tattoo would be special for anyone, but this particular one is even more special. My friend’s father has Parkinson’s disease (PD), so writing anything can be difficult for him. That “I love you” in his best handwriting is an accomplishment for him – one that my friend will take with her forever. But Parkinson’s is more than just a neurodegenerative disease that affects motor function. It also has many non-motor symptoms that are not as well-known or recognized.
Behind Alzheimer’s, Parkinson’s is the next most common neurodegenerative disorder. Average age of onset is 60 years old, and diagnosis between the ages of 20 and 50 is considered early/young-onset. The motor symptoms of Parkinson’s are the ones that are most commonly known and are obvious. These can include rigidity, tremors, gait and posture changes, difficulty speaking or swallowing, or little expression in the face. But PD is more than that; it also involves non-motor symptoms like depression, cognitive decline, rapid eye-movement sleep behavior disorder, and constipation, among others.
Important factors for diagnosis of PD include death of dopaminergic neurons and the presence of Lewy bodies. Lewy bodies are clusters of a particular protein called alpha-synuclein. When there is a mutation in any one of a number of particular genes, the alpha-synuclein protein can misfold. This means that it does not form into the correct shape and is then prone to cluster together and form the Lewy bodies. In addition, the enzymes used to clean up these unwanted aggregation of proteins do not work correctly so the Lewy bodies continue to accumulate. Eventually this leads to oxidative stress in the mitochondria and, finally, death of the neuron. PD is not as “simple” as that, however. There are multiple pathways that can cause the neurodegeneration, which is what makes PD so complicated and difficult to understand. Glutamate excitotoxicity is also thought to play a large role in PD. When there is too much glutamate in the body, it over-activates certain receptors that can lead to a huge influx of calcium into the cell. When there is too much calcium, the mitochondria again become stressed and cell death occurs. Inflammation in the brain has been linked to PD, as well. When there is inflammation, certain substances are produced, called cytokines. These cytokines then cause increased production of reactive oxygen species, which cause oxidative stress.
Because Parkinson’s follows so many pathways, it can be difficult to treat. Some research even suggests that PD is more of an umbrella, and full-blown PD is actually a syndrome encompassing several “diseases.” Risk factors for developing PD include age, genetics, and environmental factors. There is no cure for PD, and treatment can be difficult. Generally, MAO-B (monoamine oxidase B) inhibitors are used to prevent the breakdown of dopamine in the body. The two MAOIs used most commonly are selegiline and rasagiline. MAIOs are usually used alone in early PD and then used in combination with levodopa – another drug that helps increase dopamine levels – in later PD. Treatment usually helps with the motor symptoms of PD but has little effect on the non-motor symptoms.
Since Parkinson’s disease is one that is not completely understood, it is important that we continue research in finding what is causing this neurodegeneration to begin with and better ways to treat the disease.
The Many Pathways of Parkinson’s
