Indirect evidence suggested that long polyglutamine peptides can form stable helices, a novel tubular singlestranded helix with an inner wall containing a network of peptide backbone hydrogen bonds. The difference is one of degrees, though, rather than of kind.Huntingtin, however, is a different kind of peptide.This was observed in the comparative analyses of the primary sequences. Ascertaining the structure of the Flurbiprofen aggregates has proved to be a challenge.High resolution structural analysis of the aggregates has proven difcult to date because the brils are noncrystalline and do not provide clear NMR signals without special labeling techniques.Still, some advances have been made in ascertaining structure of the aggregates, especially for A aggregates.Crosssectional analysis of electron microscope images of aggregated A imputed a structural model of amyloid brils as an assembly of three to six laterally associated laments.More detailed structural information was obtained in several studies employing atomic force microscopy.These studies yielded images of proto laments, thin. These studies indicate that lateral association of several protolaments produces the largerdiameter amyloid brils.There are striking differences in conformation between A monomer and aggregate.In contrast to the conformational exibility of the monomer, about half of the amide protons in multimeric A brils are highlyresistant to solvent exchange is competent to form brils, and deletion of this core from A abrogates bril formation. Xray diffraction studies combined with molecular modeling produced a detailed structure of A brils: a hairpin with a turn at residues, an antiparallel arrangement of strands perpendicular to the long axis of the ber, forming continuous sheets, and intersheet interactions forming the laments. However, the applicability of this structural model to Posaconazole fulllength A has been challenged by more recent solidstate NMR studies.A detailed examination of A brils produced the surprising result that A forms parallel sheets, with no turns and with like residues inregister. Multiplequantum solidstate NMR on fulllength A further supported a parallel, inregister arrangement of A monomers in the brils, with the parallel arrangement extending over at least four peptide chains. The biological relevance of these in vitro studies has been questioned; in animals with scrapie, for example, amyloid aggregates are not always observed.These reports demonstrate that peptides with long polyglutamine stretches can be induced to form amyloid aggregates in vitro.There remains a great deal to learn about the ultrastructure of htt aggregates.There is limited evidence that the in vivo nuclear inclusions have amyloidlike properties. Broadly speaking, there are two schools of thought: the nucleationelongation model and the templateassisted model.In the nucleationelongation model, initial selfassembly is slow and unfavorable until a critical size is reached.Once the nucleus is formed, further elongation by addition of monomers is rapid.In the templateassisted model, exposure of the monomer to an aggregate catalyzes a conformational change of the non monomer into a rich form that is aggregation prone.Roughly equivalent to the nucleationelongation versus templateassisted models, one can consider whether peptide selfassembly is spontaneous or induced.Experimental and modeling efforts are briey reviewed to see what evidence exists for either model of peptide assembly.Spontaneous conversion of soluble A monomer to amyloid is easily achieved in neutral or slightly acidic buffers containing physiologically relevant salt concentrations.