PD is recognized as one of the most common neurological disorders, affecting approximately 1% of individuals older than 60 years. Common features include resting tremor, rigidity, bradykinesia, and postural instability. The incidence has been estimated to be 4.5-21 cases per 100,000 population per year. PD is about 1.5 times more common in men than in women. The incidence and prevalence of PD increase with age. The average age of onset is approximately 60 years. Onset in persons younger than 40 years is relatively uncommon. This disease is not contagious.
What happens?
The cause of PD is unknown although there are many theories. It is caused due to lack of dopamine in their brain (dopamine is a neurotransmitter that carries messages from one nerve cell to another) because the cells that manufacture this important chemical messenger have either been lost or blocked.
PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Approximately 60-80% of dopaminergic neurons are lost before clinical symptoms of PD emerge. Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain. There the cells release dopamine, an essential neurotransmitter. Loss of dopamine in the corpus striata is the primary defect in Parkinson's disease.
Dopamine is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine negatively affects the nerves and muscles controlling movement and coordination, resulting in the major symptoms characteristic of Parkinson's disease.
The disease process also may impair nerve endings in the heart that regulate the release of norepinephrine, a hormone that regulates blood pressure, pulse rate, perspiration, and other automatic responses to stress.
One theory concerning why these cells are destroyed states that as we age the liver loses its efficiency, and the cells are destroyed by the toxins that the less efficient liver can't filter out or detoxify. Others believe that environmental toxins such as pesticides or other chemicals and genetics play a part. Free radical damage may also play a part in Parkinson's as free radicals steal electrons allowing dopamine to be lost through oxidation.
The Biologic Factors:
Abnormal Apoptosis (Programmed Cell Death). Cells in the body are programmed to naturally die through a genetically regulated process called apoptosis. There is evidence that in PD, this process goes awry in nerve cells.
Proteins Involved in PD. Research suggests that three molecules are critical in the development of inherited PD: parkin, alpha synuclein (specifically alphaSp22), and ubiquitin, which all interact in the normal brain. AlphaSp22 is produced in the nerve cells involved with the dopamine pathway. Parkin normally causes alpha synuclein to bind with a molecule called ubiquitin, which then triggers apoptosis causing this compound to self-destruct. In many cases of inherited Parkinson's disease, however, parkin is abnormal and fails to bind alpha synuclein to ubiquitin. Apoptosis does not take place and, instead of dying, synuclein accumulates in Lewy bodies, deposits of fibrous tissue found in all patients with PD.
Lewy Bodies. Fibrous deposits known as Lewy bodies are the hallmark signs of Parkinson's disease. They are found in the substantia nigra, the place in the brain where dopamine is first released. It is not clear whether Lewy bodies are the major killers of the nerve cells or whether they are simply a byproduct of the degenerative process. They are found not only in the brains of patients with PD, but in rare cases, may show up in cells in other parts of the body (the heart, intestine), causing severe disabling symptoms. These substances are also present in other diseases that cause dementia, such as Alzheimer's, and can occur in people without neurologic symptoms.
Complex I and Oxygen Free Radicals. Some research has observed that certain Parkinson's patients have a 30% to 40% reduction in an enzyme called complex I. This enzyme is found in the mitochondria, structures in cells that generate energy. Some theories suggest that low amounts may make nerve cells vulnerable to the assault of oxygen free radicals (also called oxidants). Oxi
