Thanks for the link to the paper. Here are some quotes from the paper:
" Aging processes lead to an increase in the amount of iron in brain tissue. This physiological process could compromise the iron homeostatic system [51], leading to an excess of iron that is not efficiently chelated by iron proteins."
“In agreement, recently, the treatment of four NF patients with the BBB permeable iron-chelator deferiprone (DFP) resulted in a positive clinical outcome [106]. In one case, the authors were able to revert symptoms after a few months of treatment, showing that the earlier the treatment was initiated, the better the results on disease progression were.”
“Given that the iron chelator does not modify the diseases suggests the noncausal role of iron in most neurodegenerative diseases, but it should be kept in mind that the iron accumulation process is very slow, and when it becomes evident, neuronal death has already occurred. Therefore, treatment with chelators is performed when the damage is already severe and difficult to recover. An alternative explanation for the limited success of chelation therapies can be ascribed to the involvement of multiple iron roles: iron assumes a crucial role not only in neurotransmitter synthesis, primarily dopamine, but also in synaptic plasticity. Disrupting concurrently these two pathways, it is not surprising that improvements are not observed, but rather cognitive deterioration occurs.”
What they say above suggests to me that chelation therapy doesn’t work in neurodegenerative diseases, not necessarily because the chelation therapy doesn’t reduce brain iron but because the damage resulting from the excess iron is already done and won’t be reversed by reducing iron levels. That said, I don’t see them claim that chelation therapy effectively removes brain iron, so they don’t rule out the possibility that difficulty in chelating iron from the brain is a problem. In fact, in the first quote above, they claim that excess brain iron may not be easily chelatd by iron proteins. What they mean by “iron proteins” here is not clear but checking reference 51 (PMID: 12208347) They appear to be talking about lipofuscin.
Lipofuscin is well known to accumulate in cells with aging and while lipofuscin is not inherently an iron containing material, it does bind to iron and the bound iron results in oxidative stress. Since lipofuscin is not easily removed by the body, perhaps when they refer to brain iron not being easily chelated they are talking about accumuluation of lipofuscin and the iron that gets bound to it. That would make senses to me. In that case, the lipofuscin accumulation probably depends in part on cumulative exposure to excess iron so people that have excessive iron for extended periods of time, may have increased levels of lipofuscin (and consequently iron bound to lipofuscin) in their brains, and this is not reversible by chelation but can merely be slowed down by chelation.
