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These islet amyloid deposits of IAPP are believed to be a major contributor to β-cell failure. 1 the amyloidogenic proteins are anomalous deposits built from nonamyloidogenic precursors or from fragments thereof. In order to probe further what has occurred to produce the anomalous deposits one has to examine the atomic level structure of the proteins. This requires using more powerful techniques than light or electron microscopy. The paramount experimental techniques for exploring protein structure at atomic level of detail are X-ray crystallography and nuclear magnetic resonance (NMR).

Clarke, M. C. (1967). Does the agent of scrapie replicate without nucleic acid? Nature, 214, 764–766. , & Soto, C. (2005). In vitro generation of infectious scrapie prions. Cell, 121, 195–206. Deleault, N. , Harris, B. , Rees, J. , & Supattapone, S. (2007). Formation of native prions from minimal components in vitro. Proceedings of the National Academy of Sciences of the United States of America, 104, 9741–9746. 28 1 Introduction Gajdusek, D. , Gibbs, C. , & Alpers, M. (1966). Experimental transmission of a kuru-like syndrome to chimpanzees.

Mutant alleles are designated by the abbreviation mt and wild type by wt. Probands are identified by arrows. Blue diamonds denote ALS, orange FTD, and green both ALS and FTD in the same individual (adapted from Renton Neuron 72: 257 © 2011 Reprinted by permission from Elsevier) in sarcoma (FUS) were discovered to be present in a substantial fraction of the intracellular inclusions observed in not only ALS but also in frontotemporal lobar degeneration (FTLD). Mutations in these two proteins could directly account for another 10 % of the instances of FALS cases and some of the nonfamilial, or sporadic, cases, too.

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