Navigation Links
Iron is involved in prion disease-associated neuronal demise

Imbalance of iron homeostasis is a common feature of prion disease-affected human, mouse, and hamster brains, according to a new study by Dr. Neena Singh and colleagues at Case Western Reserve University School of Medicine, alongside collaborators from Creighton University. These findings, published March 13 in the open-access journal PLoS Pathogens, provide new insight into the mechanism of neurotoxicity in prion disorders, and novel avenues for the development of therapeutic strategies.

Unlike other neurodegenerative conditions, prion disorders are sporadic, inherited, and infectious, and affect both humans and animals; common examples are mad cow disease in cattle, scrapie in sheep, and Creutzfeldt-Jakob disease in humans. The causative agent is a misfolded protein referred to as PrP-scrapie that replicates itself by changing the conformation of neighboring copies of the same protein, namely the prion protein. Aggregates of PrP-scrapie are toxic to brain cells and cause a spongy-like appearance in diseased brains.

Research from the Singh laboratory suggests that accumulation of PrP-scrapie alters the metabolism of iron in diseased brains. The imbalance of brain iron homeostasis worsens with disease progression, and is not an outcome of end-stage disease. Since iron is highly toxic when mismanaged, this condition is likely to contribute significantly to prion-disease-associated neurotoxicity. The likely cause of this condition is loss of normal function of the prion protein in cellular iron metabolism demonstrated recently by Singh and colleagues, combined with gain of toxic function by the redox-active PrP-scrapie complex as shown in this report.

Singh and her team were surprised to find that prion disease-affected brains are iron deficient despite a significant increase in their overall iron content. The group concludes that ferritin, a major iron storage protein, co-aggregates with PrP-scrapie in diseased brains and sequesters bound iron in the complex, creating a state of apparent iron deficiency. The brain cells respond to this condition by increasing their level of iron uptake, thus creating a vicious cycle of increased iron uptake in the presence of increased iron.

These observations contribute to our understanding of how the prion agent causes neurotoxicity, and may enable the development of novel therapeutic strategies targeted at restoring brain iron homeostasis in prion disorders.


Contact: Dr. Neena Singh
Public Library of Science

Related biology news :

1. U-M researchers ID gene involved in pancreatic cancer
2. Researchers uncover obesity gene involved in weight gain response to high-fat diet
3. UT Southwestern researchers disrupt biochemical system involved in cancer, degenerative disease
4. Ancient African exodus mostly involved men, geneticists find
5. More findings on gene involved in childhood asthma
6. Columbia geneticists uncover new gene involved in determining hair texture and density in humans
7. Family ties that bind: Maternal grandparents are more involved in the lives of their grandchildren
8. Nationwide Childrens Hospital involved in expanded access program for treatment of PKU
9. New study shows greenback cutthroat trout involved in recovery effort misidentified
10. Researchers identify proteins involved in new neurodegenerative syndrome
11. Common soil mineral degrades the nearly indestructible prion
Post Your Comments:
(Date:4/11/2017)... Research and Markets has announced the addition of the ... ... grow at a CAGR of 30.37% during the period 2017-2021. ... prepared based on an in-depth market analysis with inputs from industry ... over the coming years. The report also includes a discussion of ...
(Date:4/6/2017)... April 6, 2017 Forecasts by ... Document Readers, by End-Use (Transportation & Logistics, Government & ... Gas & Fossil Generation Facility, Nuclear Power), Industrial, Retail, ... Are you looking for a definitive report ... ...
(Date:4/5/2017)... KEY FINDINGS The global market for stem ... 25.76% during the forecast period of 2017-2025. The rise ... growth of the stem cell market. Download ... The global stem cell market is segmented on the ... cell market of the product is segmented into adult ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... ... October 10, 2017 , ... ... program has won a US2020 STEM Mentoring Award. Representatives of the FirstHand program ... in Volunteer Experience from US2020. , US2020’s mission is to change the trajectory ...
(Date:10/10/2017)... (PRWEB) , ... October 10, 2017 , ... ... innovation and business process optimization firm for the life sciences and healthcare industries, ... conference in San Francisco. , The presentation, “Automating GxP Validation for Agile ...
(Date:10/9/2017)... , ... October 09, 2017 , ... At its national ... Christopher Stubbs, a professor in Harvard University’s Departments of Physics and Astronomy, has been ... a member of the winning team for the 2015 Breakthrough Prize in Fundamental physics ...
(Date:10/7/2017)... ... October 06, 2017 , ... ... Hi-C-based genomic technologies, launched its ProxiMeta™ Hi-C metagenome deconvolution product, featuring the ... and accompanying cloud-based bioinformatics software to perform Hi-C metagenome deconvolution using their ...
Breaking Biology Technology: