title: Nanoscale studies link amyloid maturity with polyglutamine diseases onset.
abstract: The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington's disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.
authors: Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|Department of Chemistry, University of Cambridge, CB21EW, United Kingdom.
authors: F S
authors: FS
authors: Ruggeri
authors: Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: S
authors: S
authors: Vieweg
authors: Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: U
authors: U
authors: Cendrowska
authors: Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: G
authors: G
authors: Longo
authors: Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: A
authors: A
authors: Chiki
authors: Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|Qatar Biomedical Research Institute (QBRI), Hamad Bin Kahlifa University (HBKU), P.O Box 5825, Doha, Qatar.
authors: H A
authors: HA
authors: Lashuel
authors: Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors: G
authors: G
authors: Dietler
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein / Q000737:chemistry* / Q000378:metabolism; D006816:Huntington Disease; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D066263:Protein Aggregation, Pathological
chemical_list: D000682:Amyloid; C086055:HTT protein, human; D000071058:Huntingtin Protein; D010455:Peptides; C097188:polyglutamine