Am looking for a key gene or whole pathway which regulate the metal induced Neuro degenerative diseases in wistar albino rat.
The gene for the divalent metal ion transporter is what I would look at as this regulates the deposition of heavy metals such as iron and manganese.
Most of the transition metals are neurotoxic but only manganese produces symptoms resembling Parkinson's. As far as I know there is no information available on the valence state of the toxic form (II, IV or VII)). High levels of serum Mn produce a condition called manganism. The symptoms do not abate when Mn levels fall to normal levels but remain and continue to worsen. This suggest that Mn instigates the conversion (misfolding) of a neuroprotein (α-synuclein?) to a prion-like form.
I don't think enough is known to look for a specific gene yet. You might find a clue by comparing individuals matched for age, exposure and lifestyle, who work in the manganese extraction industry (where most cases of manganism occur) and try to find out whether some have higher Mn levels than others and, if so, whether there is a genetic factor at work and whether there is a relation between serum Mn level and the risk of contracting manganism.
If it is too difficult to deal with the extractive industry another source of possible material would be those who have had metal implants - especially hips. 23andMe reported in April 2012 that 25% of PD patients had had joint surgery but 23andMe had no further information (I asked them). Most clinicians say that it isn't surprising because P(eople)w(ith)P(arkinson's) usually have joint problems (which is not true, but they do fall over a lot, which can break off the neck of the femur, necessitating a hip replacement).
I would like to screen a hundred or two PWP and a similar number of controls for serum transition metals but this is not so easy because (1) the average GP has 2000-2500 patients of which only about 5 have PD; (2) Taking blood is a big issue and you'd need approval from an Ethics Committee and (3) most medical labs use spectrophotometry for metals analysis, which is not sensitive enough and you have to find one that uses ICP-MS.
There is a lot of information about metals and neurotoxicity and I could easily overwhelm you with stuff you don't need. So the question is ..... what lies behind your question?
I had a metal hip resurface in 2003 and was diagnosed with a Parkinson's Spectrum Disorder in 2010. hence my interest .....
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