[lou_lou]

Causes:

The etiology of Parkinson disease is largely unknown in most patients. However, evidence does exist for both genetic and environmental causes. In the United States, rural residence, exposure to well water, and prior use of pesticides are environmental factors that have been found to be associated with an increased risk of developing Parkinson disease.
Genetic factors also may be important in the pathogenesis of the disease. A positive family history is found in approximately 15-20% of patients with idiopathic Parkinson disease, but the mutation or mutations responsible in most cases are not identified.

Currently, 5 different genetic mutations have been found to cause autosomal dominantly inherited Parkinson disease. These are generally rare, although one condition, PARK8, has been described in up to 5% of families with Parkinson disease and a dominantly inherited pattern.

Three autosomal recessive forms are also known. Of these 3 forms, PARK2 (the parkin mutation), may be responsible for familial Parkinson disease in other inheritance patterns and is the most common form of genetically inherited disease that has been recognized to date.
Although considered rare, mutations in the gene coding for the protein parkin (termed PARK2) may be more common than previously thought and may account for a large number of patients with young-onset Parkinson disease.

This mutation was originally described in patients with juvenile parkinsonism, and it was described as an autosomal recessive condition. However, PARK2 may be an autosomal dominant or semidominant condition, causing disease onset in middle age. In one series of patients with sporadic disease and onset before age 40 years, 18% of patients had a mutation in this gene. Most patients were heterozygous, ie, they had one normal and one abnormal parkin gene.

In another study involving families with 2 or more siblings with Parkinson disease, a mutation in this gene was found in 18% of the patients. One third of affected members of these families had mutations in both parkin genes; the other two thirds had one normal parkin gene. This study also found that the patients with 2 abnormal genes had earlier disease onset, suggesting that there may be a "dose effect" in having 1 or 2 mutated parkin genes. The study also indicated that some patients had disease onset at or older than age 60 years, suggesting that a mutation in the parkin gene can cause Parkinson disease that can start at an age typical of sporadic Parkinson disease.
Dopa-responsive dystonia, discussed in more detail in another article, is due to a one of two different mutations. The more common form, which occurs in an autosomal dominant inheritance pattern, is due to a mutation in a gene coding for the enzyme GTP-cyclohydrolase (GTPCH), which is involved in the synthesis of tetrahydrobiopterin, a cofactor needed for the enzyme tyrosine hydroxylase. A less common autosomal recessive form, due to a partial deficiency in tyrosine hydroxylase, also occurs. As partial penetrance and new mutations have been described in patients with GTPCH-1 deficiency, a family history may not be present. In these disorders, dopamine is depleted in the striatum, but no cell degeneration occurs. Interestingly, a recent study reported that 3 of 10 families thought to have dopa-responsive dystonia actually had a mutation in the parkin gene instead, further illustrating the clinical overlap in these conditions.
The biochemical basis for cell degeneration is unknown. However, evidence exists that patients with Parkinson disease have a deficiency of the mitochondrial enzyme complex I in the midbrain. In cell culture and animal models, inhibitors of complex I enhance oxidant or excitatory amino acid toxicity to dopaminergic neurons.

http://www.emedicine.com/neuro/topic635.htm#target1

[lindylanka]

Thanks for this article, Tena, it is of great interest to me. You do such a good job of bringing so much information to us all. I really miss having the old archives, but can see a day when this forum has an accumulation of info too.

Best wishes for the new year
Lindy

[lou_lou]

Thank You dear lindy for the kind words...
I appreciate your feedback.

I try to share anything that helps me, hoping it may help someone
have a better day, I am always thankful for good information, and I
forget to thank the researchers, which in a way is what we are,
we are pioneering something for future generations, we are giving real insight into "Parkinson's Disease".