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- Title
Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration.
- Authors
Walsh, Dominic M; Selkoe, Dennis J
- Abstract
Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein fibrils characterize many different neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, Huntington's disease, and the transmissible 'prion' dementias. There is strong evidence from genetic, transgenic mouse and biochemical studies to support the idea that the accumulation of protein aggregates in the brain plays a seminal role in the pathogenesis of these diseases. How monomeric proteins ultimately convert to highly polymeric deposits is unknown. However, studies employing, synthetic, cell-derived and purified recombinant proteins suggest that amyloid proteins first come together to form soluble low n-oligomers. Further association of these oligomers results in higher molecular weight assemblies including so-called 'protofibrils' and 'ADDLs' and these eventually exceed solubility limits until, finally, they are deposited as amyloid fibrils. With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction.
- Publication
Protein and peptide letters, 2004, Vol 11, Issue 3, p213
- ISSN
0929-8665
- Publication type
Journal Article
- DOI
10.2174/0929866043407174