Abstract |
The aggregation of misfolded proteins has long been regarded as a pathological event in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the exact molecular mechanisms that govern protein metabolism that may lead to toxicity remain largely unclear. Originally targeted as the causative agent, it has since become evident that aggregation formation may not be necessary for disease progression and studies show that they may even serve functional and protective roles. Although the focus has since shifted to the toxicity of intermediate protein species preceding aggregation formation, many questions remain: Is the blame for the neural destruction to be put on one event alone, or rather on a state of cellular disequilibrium resulting from multiple events? If the cause is multifactorial, then what triggers the toxic cascade and how can this be targeted therapeutically? In order to understand the origin of toxicity, the exact underlying mechanism and impact of each contributing process must be assessed. Therefore, the structural properties, mechanism of formation, cytotoxic and/or protective effects, as well as the clinical impact of protein intermediates and aggregates will be reviewed here with the goal to establish a neurodegenerative disease model aimed at improving current therapeutics, which may ultimately contribute towards improved treatment modalities.
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Authors | Chrisna Swart, William Haylett, Craig Kinnear, Glynis Johnson, Soraya Bardien, Ben Loos |
Journal | Experimental gerontology
(Exp Gerontol)
Vol. 58
Pg. 279-91
(Oct 2014)
ISSN: 1873-6815 [Electronic] England |
PMID | 25219768
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Nerve Tissue Proteins
- Protein Aggregates
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Topics |
- Animals
- Homeostasis
- Humans
- Nerve Tissue Proteins
(chemistry, metabolism)
- Neurodegenerative Diseases
(metabolism, pathology)
- Protein Aggregates
- Protein Aggregation, Pathological
- Proteostasis Deficiencies
(metabolism, pathology)
- Signal Transduction
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