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From: "Dr. Jeffrey Tosk" <[log in to unmask]> Subject: Hallervorden-Spatz I n response to JR Breman's comments....Iron is not the agent responsible for the dark color of the substantia nigra....the pigment neuromelanin is responsible . Neuromelanin is a polymer of dopamine. It is related to the melanin that colors hair, skin and eyes. At these sites melanin is well known to protect these tissues against the damaging effects of light. Much of my research in PD it focused on understanding the structure of NM in PD. As many of you know, NM is all be depleated in the parkinsonian nigra. The nigra in PD appears bleached clean and clear. The relationship between NM and iron is very interesting. Neuromelanin binds incredable quantities of iron and other metal ions. In Hallervorden-Spatz the iron lost from other midbrain sites probably is chelated by the nigral melanin. It is interesting that the nigra and other midbrans structures contains more iron (per gram tissue) then does liver - the major site for iron storage. In any case when the levels of free and melanin-bound iron build up, a series of nasty oxidation reactions place this area under great stress....a simple>model (very simple) would be to say that it's like "rusting" of the midbrain. Aside from surgical or direct examination, magnetic resonance imaging (mri) is very helpful for studies of brain iron and brain iron overload in PD and HS disease. The appearance of the nigra is rather dark, as is the globus in a so called T2-weighted mri of these structures. Interestingly, neuromelanin adds somewhat to the mri of the nigra since it is in fact a "stable" free radical and can interact with the iron (also free radical-like since it contains unpaired electrons). These circumstances make the detailed study of NM a natural in PD research. You may also be interested to know that MPTP of frozen addict fame targets the nigra via a very strong binding with neuromelanin.....interesting stuff, I think. Unfortunatly using this sort of information to study HS wont get one real far....the role of NM and iron are not (yet) paradigms in HS research. Jeffrey Tosk, Ph.D. ([log in to unmask])