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Prion protein and metal interaction: physiological and pathological implications.
- Source :
-
Current issues in molecular biology [Curr Issues Mol Biol] 2010; Vol. 12 (2), pp. 99-107. Date of Electronic Publication: 2009 Sep 18. - Publication Year :
- 2010
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Abstract
- Metal induced free radicals are important mediators of neurotoxicity in several neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Similar evidence is now emerging for prion diseases, a group of neurodegenerative disorders of humans and animals. The main pathogenic agent in all prion disorders is PrP-scrapie (PrP(Sc)), a beta-sheet rich isoform of a normal cell surface glycoprotein known as the prion protein (PrP(C)). Deposits of PrP(Sc) in the brain parenchyma are believed to induce neurotoxicity through poorly understood mechanisms. Recent reports suggest that imbalance of brain metal homeostasis is a significant cause of PrP(Sc)-associated neurotoxicity, though the underlying mechanisms are difficult to explain based on existing information. Proposed hypotheses include a functional role for PrP(C) in metal metabolism, and loss of this function due to aggregation to the disease associated PrP(Sc) form as the cause of brain metal imbalance. Other views suggest gain of toxic function by PrP(Sc) due to sequestration of PrP(C)-associated metals within the aggregates, resulting in the generation of redox-active PrP(Sc) complexes. The physiological implications of some PrP(C)-metal interactions are known, while others are still unclear. The pathological implications of PrP(C)-metal interaction include metal-induced oxidative damage, and in some instances conversion of PrP(C) to a PrP(Sc)-like form. Despite its significance, only limited information is available on PrP-metal interaction and its implications on prion disease pathogenesis. In this review, we summarize the physiological significance and pathological implications of PrP-metal interaction on prion disease pathogenesis.
- Subjects :
- Animals
Humans
Models, Biological
PrPSc Proteins chemistry
PrPSc Proteins genetics
PrPSc Proteins metabolism
Prion Diseases etiology
Prion Diseases genetics
Prions chemistry
Prions genetics
Protein Binding genetics
Protein Binding physiology
Metals metabolism
Prion Diseases metabolism
Prions metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1467-3045
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Current issues in molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 19767653