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:2/2/2016)... MOUNTAIN VIEW, Calif. , Feb. 2, 2016 ... diabetic retinopathy market, Frost & Sullivan recognizes US-based ... North America Frost & Sullivan Award for New ... technology provider in North America ... standard in the rapidly growing diabetic retinopathy market. ...
(Date:1/28/2016)... SAN JOSE, Calif., Jan. 28, 2016 Synaptics (NASDAQ: ... financial results for its second quarter ended December 31, 2015. ... the second quarter of fiscal 2016 increased 2 percent compared to ... the second quarter of fiscal 2016 was $35.0 million, or $0.93 ... Non-GAAP net income for the first quarter of fiscal 2016 ...
(Date:1/22/2016)... January 22, 2016 ... addition of the  "Global Behavioral Biometric ... --> http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) has ... Behavioral Biometric Market 2016-2020"  report to ... and Markets ( http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) has announced ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... Germany and GERMANTOWN, Maryland ... QGEN ; Frankfurt Prime Standard: QIA) today announced the ... Panels for gene expression profiling, expanding QIAGEN,s portfolio of ... panels enable researchers to select from over 20,000 human ... discover interactions between genes, cellular phenotypes and disease processes. ...
(Date:2/11/2016)... , Feb. 11, 2016  Wellcentive today ... Portland, Oregon -based community care ... provide population health analytics, quality reporting and care ... FamilyCare strengthen its team of quality managers, analysts ... to the provider groups serving FamilyCare members. ...
(Date:2/11/2016)... February 11, 2016 ... or "Company") (OTCQB: PSID), a life sciences company ... its Thermomedics subsidiary, which markets the Caregiver® FDA-cleared ... plan in January 2016, including entering into agreements ... monthly sales growth, and establishing several near-term pipeline ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... has announced a new agreement with Bankok,Thailand-based Global Stem Cells Network (GSCN) to ... in 15 Latin American countries, including Mexico, Costa Rica, Dominican Republic, Colombia, Argentina, ...
Breaking Biology Technology: