- Title
- Alzheimer’s disease: making sense of the stress
- Creator
- Whiteley, Chris G
- Date
- 2016
- Type
- text
- Type
- book
- Identifier
- http://hdl.handle.net/10962/67072
- Identifier
- vital:29029
- Identifier
- http://www.smgebooks.com/alzheimers-disease/chapters/ALZD-16-08.pdf
- Description
- publisher version
- Description
- To facilitate a deep understanding of the mechanisms involved in neurodegeneration and Alzheimer’s disease fundamental knowledge is required about the action and function of enzymes in the brain that not only metabolise arginine (neuronal nitric oxide synthase) but are closely associated with oxidative (superoxide dismutase; catalase; glutathione peroxidase) and/or nitrosative stress. In particular the focus extends towards enzymes that contribute to amyloid peptide aggregation and senile plaquedeposits (fibrillogenesis). Of special importance are the glycine zipper regions within these amyloid peptides, especially Aβ25-29 and Aβ29-33 (that contains two isoleucine residues) and the pentapeptide Aβ17-21 (that contains two phenylalanines), each generated by enzymatic cleavage of the intramembrane amyloid precursor protein. Use of antisense-sense technology has identified regions in each enzyme that are capable of binding with the amyloid peptides. After an initial inhibition of each enzyme there is an oligomerisation into soluble fibrils which accumulate and eventually precipitate. The use of nanoparticles do not just prevent but reverse the formation of these fibrils either by disrupting the binary adduct – enzyme-Aβ-peptide- or by reaction with, and therefore deplete, Aβ-monomers in solution and so block potential aggregation sites on the enzyme itself. Future therapy towards Alzheimer’s disease should target the C-terminal region of the amyloid precursor protein and substitute hydrophobic residues for the glycine amino acids within the glycine zipper region.
- Format
- 29 pages, pdf
- Publisher
- SM Online Publishers LLC
- Language
- English
- Relation
- Alzheimer's Disease, Whiteley, C.G. (2016) Alzheimer’s disease: making sense of the stress. In: Paz-y-Miño, C., García-Cárdenas, J.M. and Brewer, G.J. (Ed.), Alzheimer's Disease. SM Online Publishers LLC. ISBN-9781944685980, Alzheimer's Disease volume number 1 29 November 2016 9781944685980
- Rights
- Whiteley, C G
- Rights
- This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited
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Whiteley, Christopher (Emeritus Prof)
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