α-Synuclein expression is modulated at the translational level by iron.

NEUROREPORT(2012)

Cited 84|Views9
No score
Abstract
Several studies have suggested an interaction between alpha-synuclein protein and iron in Parkinson's disease. The presence of iron together with alpha-synuclein in Lewy bodies, the increase of iron in the substantia nigra and the correlation between polymorphism of the several genes implicated in iron metabolism and Parkinson's disease, support a role for iron in the neurodegeneration. Analysis of post mortem brains revealed increased amount of insoluble alpha-synuclein protein despite unchanged/reduced levels of alpha-synuclein mRNA in Parkinson's disease. Interestingly, on the basis of the presence of a putative iron responsive element in the 5'-UTR, it has been suggested that there is a possible iron-dependent translational control of human alpha-synuclein mRNA. Considering the similarity between the sequences present in human alpha-synuclein mRNA and the ferritin iron responsive element, we postulated that iron deficiency would decrease the translation of alpha-synuclein mRNA. Here we used HEK293 cells treated with iron chelator deferoxamine or ferric ammonium citrate to verify the possible iron-dependent translational control of human alpha-synuclein biosynthesis. We show that the amount of polysome-associated endogenous human alpha-synuclein mRNA decreases in presence of deferoxamine. Our data demonstrate that human alpha-synuclein expression is regulated by iron mainly at the translational level. This result not only supports a role for iron in the translational control of alpha-synuclein expression, but also suggests that iron chelation may be a valid approach to control alpha-synuclein levels in the brain. NeuroReport 23: 576-580 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
More
Translated text
Key words
deferoxamine,HEK293,iron-responsive element,Parkinson's disease,polysomes
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined