Question

The cytosolic aryl sulfotransferase genes SULT1A3 and SULT1A4 are located on chromosome 16p11.2 in a region of chromosomal instability. SULT1A3/4 are important enzymes in the metabolism of catecholamines linked to neurodegenerative diseases such as Parkinson’s and Alzheimer’s. In the present study, copy number variation of the SULT1A3/4 genes in healthy individuals, as well as a cohort of Parkinson’s disease and Alzheimer’s disease patients was examined. In all subjects, SULT1A3/4 copy number varied from 1 to 10. In Alzheimer’s disease patients, there was a significantly lower copy number compared to controls, and a positive correlation between copy number and age of disease onset. By contrast, there were no differences in Parkinson’s disease patients. However, when earlyonset Parkinson’s disease was evaluated separately, there appeared to be an association with gene copy number and risk.

Hypothesize why a low SULT1A3/3 copy number is associated with Alzheimer’s disease. (7 points)

Hypothesize why SULT1A3/4 gene copy number only influences early-onset Parkinson’s disease (3 points)

What can you infer about the role catecholamine metabolism in neurodegenerative diseases? (2 points)

Answer 1

A. 1. In Alzheimers disease patient there was significantly low copy number compared to controls and a positive coreralations between copy number and age of diesese onset.

2. The gene is located on chromosome in a region of chromosomal instability.  

3. The enzymes are involved in metabolism of catecholamines linked to neurogenerative diesese Alzheimers.

4. In present study copy number variation of gene in healthy individual as well as a cohort  of Alzheimers disease patient was examined.  

5. Soluble enzyme generate electrophillically reactive metabolities from food borne compound and environmental contaminants and drugs  often resulting in carcinogenicity.

6. Expression of not only enhanced the genotoxicity but also substantially changed the organotropism.

7. Testing for the mutant gene that have been linked to early onset ALZHEIMERS may provide may certain result if showing early symptoms.  

B. 1. When early onset of Parkinsons disease was evaluated separately there appeared to be an association with gene copy number and risk.

2. enzyme facilitate xenobiotics metabolism by catalyzing the addition of sulfate conjugate on drug molecules leading to more water soluble compond.

3.enzyme catalyses sulfation is important in the regulation of biological activity of hormones and neurotransmitter.  

C. 1. Degeneration of norepinephrinegic and dopaminergic neurons suggest that catecholamines may play a central role in the neurodegeneration in Parkinsons disease.

2. Early diagnostic marker for detecting degeneration of the peripheral sympathetic nerves and proposed the hypothesis that catecholamines causes alpha synnuclein to aggregate and play an important role in disease pathogenesis.