Plant Derived Treatments and Parkinson's Disease Treatment.

Disclaimer: The information herein is for educational purposes only. You should Never attempt to utilize this information without the cooperation, help and advice
of a licensed doctor.

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disease. The incidence of PD is expected to expand with the aging of the population.
In addition to higher incidence in aged patients, you will find there's a population of patients who develop PD substantially younger in life. The so-called early onset
Parkinson’s Disease. The root pathology of PD is reduction in the dopamine producing cells in a part of the brained termed the basal ganglion. The reason dopamine
producing cells die off, particularly in a part of the basal ganglia called the substania nigra, is not really completely understood.

A number of theories have been put forth, having said that none of these theories have been definitively proven. Although loss of dopamine input to various brain
regions is the cardinal pathology in PD, the lack of dopamine is believed to start a cascade of events that leads to dys-regulation in a wide range of other,
non-dopaminergic circuits within the brain. These secondary pathways offer potential targets for primary therapy, but also may be a means to lower some of the drug
related side effects commonly found in patients who are on long term dopamine replacement therapy.

What are the signs and symptoms of Parkinson's Disease? Parkinson’s Disease is considered a movement disorder. That means that the main symptoms of the disease
will manifest as abnormal movement of muscles.

The umbrella terms used to classify these abnormal movements is called dyskinesias. This literally means abnormal motion. There are several more specific types of
dyskinesias seen in Parkinson's Disease.

One is called bradykinesia or slow movement. It is quite frequently seen in patients with Parkinson’s' Disease. Other classical dyskinesias include tremor and phenomenon
called freezing. Freezing takes place when opposing groups of muscles become active at the same time resulting in a tug or war that freezes the Parkinson’s patient in
place.
There is growing awareness of so-called non-motor signs of Parkinson’s disease. These include cognitive decline, sleep disorders (both daytime sleepiness and night
time insomnia) along with and mood and behavioral changes. These non-motor symptoms are likely linked to changes in circuits that don't directly depend on dopamine, but
are indirectly affected by the death of dopamine producing cells in the brain.

The Anatomical Pathways In the Basal Ganglia: There are two parallel pathways that comprise the circuits of the basal ganglia. The direct pathways that promotes
movements and motions and the indirect pathways which serves to brake or slow down motion and muscle activity. These competing pathways act like the gas pedal and
brakes in a car, respectively.

Loss of the dopamine producing cells in the Parkinson’s brain favor the brake over the gas pedal and results in the bradykinesia, or slowed movement seen in patient's
with Parkinson's Disease.
The Chemistry of Parkinson's Disease, Neurochemistry and Neurotransmitters: The structural schematics of the basal ganglia circuits are complex and the chemical
messengers associated with these circuits add to the complexity of the basal ganglia. As we have discussed, the loss of dopamine is the underlying cause of this
disease and it current treatment consists mainly of dopamine replacement therapy.

However the anatomical model of PD also includes other competing neurotransmitters like the inhibitory neurotransmitter GABA and also Adenosine. It uses the excitatory neurotransmitter Glutamate as well. It is quite likely that the role of a number of other neurotransmitters will be discovered as the details of the basal ganglia pathways are unraveled.

In most Parkinson’s Disease patents , at least in the short term, dopamine replacement therapy is very helpful in diminishing the dyskinesias. This article will
focus on other target neurotransmitters.
Adenosine: Current research has indicated that blocking the adenosine (A2) receptor in the brain, may down regulate the indirect pathways of the basal ganglion. Studies
of A-2 receptor specific blocker drugs are demonstrating clinical promise in the treatment of PD. The methylxanthines are herbal products with antagonistic activity at the adenosine receptors. They include caffeine, theophylline and theobromine found in coffee, tea and chocolate respectively. The A-2 receptor antagonists may provide therapeutic modulation of the indirect pathways in PD subsequently improving
bradykinesia through inhibition of this inhibitor pathway. In other words, they act to release the indirect pathway which is the brake on movement and motion.

They may at the same time reduce daytime somnolence because in addition to their suppressive effects on the indirect pathway, blockade of the A2 receptor also increase arousal in the central nervous system. The natural product, Ilex could find potential use as a beneficial natural medication if given in daytime to help improve
Parkinson’s motor symptoms and daytime sleepiness.

The herb Ilex appears to offer the best natural replacement for methylxanthines A2 receptor blockers and at least one study has revealed it could be beneficial in the
management of the symptoms of Parkinson’s Disease.

Glutamate: The complete role of glutamate in PD is unknown. Studies of glutamate receptor blockers and agonist have produced mixed results in PD patients. This may
be explained by the fact that different receptor of the glutamate family can have unique, even opposite effects within the nervous system. So glutamate may bind to
some receptors in the brain than make movements easier, but also bind to other receptors it different parts of the brain that make movements harder.

One glutamate receptor that appears to be emerging as an interesting helpful target in PD management is the Glutamate 5 metabotrophic receptor. that’s a really big word so we'll give it a nickname. This glutamate receptor also known as mGlu5 for short.

Although the study results are preliminary, early studies of mGlu5 receptor blockers in animal models of PD not show improvement in symptoms, but also suggest that
blocking this glutamate receptor might actually change the disease process itself.
If these results hold true in future studies, glutamate receptor antagonism could be the first treatment available to PD patients that can truly change the basic
pathology of the disease in addition to ameliorating its symptoms.

Down regulation of the glutaminergic pathways inside the brain could perhaps produce beneficial affects on the mood disorders, agitation, insomnia and other associated
non-motor symptoms seen in PD patients.

Pharmacognosy Substitutions: Magnolol a component of the herbal remedy Magnolia Bark has recently been shown to specifically antagonize the mGLu5 receptor. Theanine is a
glutamate receptor antagonist and functions as a glutamate analog. It is not clear if Theanine operates selectively on Glutamate receptors or if its effects are non-specific.

These natural products are in preliminary stage of study for the treatment of Parkinson's Disease Symptoms, they are very promising complimentary remedies that may
someday prove beneficial to the Parkinson’s patients.