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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Small molecule oxidation products trigger disease-associated protein misfolding.

Oxidative stress and inflammation are risk factors for both the development of alpha-synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, and Alzheimer's disease, the two most common neurodegenerative disorders. These diseases are associated with the neurotoxic deposition of misassembled alpha-synuclein and amyloid-beta (Abeta) peptides, respectively. Both occur sporadically, that is, without detectable disease-related mutations, in the vast majority of cases. Small molecule oxidation products, especially secosterols derived from cholesterol and 4-hydroxynonenal derived from lipid peroxidation, found in afflicted brains, accelerate the misassembly of both Abeta and alpha-synuclein. This Account explores the mechanism of small molecule oxidation product-mediated protein misassembly and possible intervention strategies.[1]

References

  1. Small molecule oxidation products trigger disease-associated protein misfolding. Bieschke, J., Zhang, Q., Bosco, D.A., Lerner, R.A., Powers, E.T., Wentworth, P., Kelly, J.W. Acc. Chem. Res. (2006) [Pubmed]
 
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