Navigation Links
Iron is involved in prion disease-associated neuronal demise
Date:3/13/2009

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
neena.singh@case.edu
216-368-2617
Public Library of Science
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:3/22/2016)... Ontario , PROVO and ... Newborn Screening Ontario (NSO), which operates the ... for molecular testing, and Tute Genomics and UNIConnect, ... management technology respectively, today announced the launch of a ... next-generation sequencing (NGS) testing panel. NSO ...
(Date:3/17/2016)... -- ABI Research, the leader in transformative technology ... will reach more than $30 billion by 2021, ... electronics, particularly smartphones, continue to boost the biometrics ... two billion shipments by 2021 at a 40% ... Analyst at ABI Research. "Surveillance is also gearing ...
(Date:3/14/2016)... MELBOURNE, Florida , March 14, 2016 ... on the growing mobile commerce market, announces the airing of ... York channels starting the week of March 21 st . ... and CNBC, including its popular Squawk on the Street show. ... company focused on the growing mobile commerce market, announces the ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... ... 2016 , ... Amendia, Inc., a leading designer, developer, manufacturer ... completion of a significant transaction and partnership that positions Amendia for accelerated growth ... Kohlberg & Company, L.L.C. (“Kohlberg”), a leading private equity firm specializing in middle ...
(Date:4/29/2016)... and San Diego, CA (PRWEB) , ... April 29, 2016 , ... ... Stem Cell Foundation (NSCF) to support the development of a patient-specific stem cell therapy ... Andrés Bratt-Leal in the lab of Dr. Jeanne Loring at The Scripps Research Institute ...
(Date:4/28/2016)... April 28, 2016 The report ... Brayton Cryocoolers), Service (Technical Support, Product Repairs & Refurbishment, ... Global Forecast to 2022", published by MarketsandMarkets, the global ... by 2022, at a CAGR of 7.29% between 2016 ... Tables and 94 Figures spread through 159 Pages and ...
(Date:4/28/2016)... MA (PRWEB) , ... April 28, 2016 , ... ... Asymmetrex will deliver a talk on its first-in-class technologies for tissue ... 2016 Meeting on RNAiMicroRNA Biology to Reprogramming & CRISPR-based Genome Engineering ...
Breaking Biology Technology: