Iron and α-synuclein in Parkinson’s disease

synuclein protein in Parkinson’s disease

Alpha synuclein mRNA has an iron responive element in the 5′ untranlated region. Iron responive elements in the 5′ untranlated region of mRNA when bound by iron responsive protein 1 (IRP1) or iron responive protein 2 (IRP2) destabilize transcripts of iron-regulated proteins. Increasing iron levels would decrease levels of IRP1 and IRP2 and increase levels of alpha synuclein which is held to be very bad.

Alpha synuclein can act as a ferrireductase reducing iron 3+ to iron 2+. Overexpressing human α-synuclein in nigral dopaminergic neurons demonstrated a correlation between α-synuclein expression and ferrireductase activity, however, in Parkinson’s patients there is a reduction of ferrireductase activity in brains.

What if the key fact about alpha synuclein in Parkinson’s patients is alpha synuclein aggregates form only after decreases in ferrireductase activity in Parkinson’s patients. High, constant but normal iron levels where iron levels are tightly regulated throughout the day could keep ferrireductase activity constant throughout the day preventing alpha synuclein aggregates from forming.

Supplemental iron from iron carbonyl could keep iron levels constant keeping ferrireductase activity of alpha synuclein constant preventing alpha synuclein aggregates from forming. There is no significant differences in serum iron levels between controls and Parkinson’s patients. There are serious difficulties with iron in PD patients but these difficulties could stem from a loss of iron homeostasis which could be re-regulated by iron from iron carbonyl given three times a day.

This idea would, of course, have to be tested in rats before being tested in humans

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