![]() All of these disorders are classified in a more general category of human pathologies termed protein deposition diseases which are characterized by the organization of soluble protein into β-sheet rich fibrils that are deposited in extracellular plaques or intracellular inclusions bodies. Mutated huntingtin protein aggregates into insoluble, amyloid fibrils that have structural and cytotoxic similarities to aggregates associated with other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. While 17–20 glutamines are typically found in the non-mutated protein, expression of huntingtin (Htt) protein with an elongated chain of greater than 35 uninterrupted glutamines (Q35) is associated with Huntington's disease (HD). These genetic disorders are characterized by a CAG repeat expansion in the coding region of a mutated gene and bring about an expanded polyglutamine tract in the encoded protein. Huntington's disease is an autosomal dominant neurodegenerative disorder in a family of CAG trinucleotide repeat disorders which includes Spinobulbar muscular atrophy and six types of Spinocerebellar ataxia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. ![]() This work was also supported by grants from the NINDS, the Human Frontier Science Program, and the Huntington's Disease Society of America. YS and RM were supported by the Agence Nationale de la Recherche (ANR-08-NEUR-001-01 and ANR-09-MNPS-013-01) and the CNRS. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: AMS was supported by the Stanford DARE Fellowship. Received: JAccepted: DecemPublished: January 17, 2013Ĭopyright: © 2013 Streets et al. Tufts University, United States of America The combined techniques allow elucidation of complex aggregation kinetics and are used to reveal multiple stages of amyloid fibril formation.Ĭitation: Streets AM, Sourigues Y, Kopito RR, Melki R, Quake SR (2013) Simultaneous Measurement of Amyloid Fibril Formation by Dynamic Light Scattering and Fluorescence Reveals Complex Aggregation Kinetics. Thioflavin T fluorescence reports β-sheet fibril content while dynamic light scattering measures particle size distributions. Despite the wide range of amino acid sequence in the aggregation prone polypeptides associated with these diseases, the resulting amyloids display strikingly similar physical structure, an observation which suggests a physical basis for amyloid fibril formation. These pathologies are all related by the propensity of their associated protein or polypeptide to form insoluble, β-sheet rich, amyloid fibrils. ![]() ![]() Huntington's disease is a neurodegenerative disorder in a class of human pathologies that includes Alzheimer's and Parkinson's disease. An apparatus that combines dynamic light scattering and Thioflavin T fluorescence detection is used to simultaneously probe fibril formation in polyglutamine peptides, the aggregating subunit associated with Huntington's disease, in vitro.
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