Causes and Treatments of PD
Genetics, Environment and Dysfunctional Cells All Play a Part in PD
Find out why dopamine-producing cells die in patients with PD, and how preventing this from happening is the current focus of therapy targets
Parkinson’s Disease (PD) is a nervous system disorder characterized by a loss of motor control. Symptoms of the disease include trembling in the arms and legs, muscular rigidity, and a lack of balance.
PD arises from the abnormal death rate of dopamine-producing cells in a part of the brain called the substantia nigra. Dopamine travels to another part of the brain called the striatum, where it activates nerve cells that coordinate muscle activity, meaning that a lack of dopamine will ultimately lead to abnormal motor control.
Causes
Most research points to a combination of causes of PD, including genetics, environmental factors and abnormal cellular processes.
The familial or genetic form of PD occurs in fifteen per cent of cases. Among the genes implicated in this form of the disease are parkin and ubiquitin, both of which help clear nerve cells of excess proteins. It is suspected that the inability of nerve cells to clear protein waste contributes to apoptosis (or cell death).
Possible environmental causes have pointed to certain pesticides or technological by-products, although researchers have yet to find evidence of any definitive link to a particular toxin or drug.
Dopamine-producing cells could also be destroyed due to defects in mitochondria, our cells’ power producer, or oxidative stress from either an excess of free radicals or a lack of antioxidants.
According to the U.S. National Institute of Neurological Disorders and Stroke, there is a strong link between mitochondrial dysfunction and PD. The Parkinson's Disease Research Agenda published by this organization states that “mitochondrial dysfunction has numerous consequences, including energetic failure, generation of reactive oxygen species, disregulation of calcium homeostasis and induction of apoptosis, each of which may be important in Parkinson’s disease.”
Oxidative stress occurs when free radicals attack cellular structures. A study by researchers at the Buck Institute for Age Research, published in December 2007 in The Journal of Neuroscience, showed that the degeneration of cells in the substantia nigra is linked to lower levels of glutathione, a principal antioxidant in the body.
Treating PD
Simply giving patients dopamine will not counteract the effects of the disease, as very little dopamine can cross the blood-brain barrier.
Levodopa is currently the most effective antiparkinson drug, as it is transformed into dopamine in the brain. However, most of the drug (95%) is broken down into dopamine before reaching the brain, which can cause untoward reactions in many people, such as nausea, vomiting and dyskinesia.
Dopamine agonists, such as ropinorole, mimic the effects of dopamine, in that they activate nerve cells in the striatum.
Treating PD with surgery was more common before the advent of drug therapies. However, a surgical procedure such as deep-brain stimulation is still considered as a viable option for PD patients. Complementary and alternative medicine treatments can also provide different ways to alleviate symptoms.
Preventing PD
As in other degenerative diseases, such as Alzheimer’s, a prime treatment goal is prevention, as once a patient has reached the stage where symptoms can be diagnosed, cell death is already substantial and irreversible.
One prevention method would be to “fix” or replace mutated genes, such as parkin and ubiquitin, in order to maintain the cellular protein degradation process, thereby keeping cells alive longer.
A study by scientists at Emory University School of Medicine published in PLoS Biology in June 2007 found that a gene called PINK1, which has been implicated in PD-related cell death, protects against cellular oxidative stress.
The study on glutathione mentioned above by researchers at the Buck Institute for Age Research also showed that when mice with a genetic predisposition to PD are “pre-treated” with antioxidants before being exposed to specific environmental toxins, the antioxidant treatment actually lessens the impact of the toxic exposure.
References:
National Institute of Neurological Disorders and Stroke. Parkinson's Disease Research Agenda. Accessed January 12, 2008
