title: Structural evidence for alpha-synuclein fibrils using in situ atomic force microscopy.
abstract: Human alpha-synuclein is a presynaptic terminal protein and can form insoluble fibrils that are believed to play an important role in the pathogenesis of several neurodegenerative diseases such as Parkinson's disease, dementia with Lewy bodies and Lewy body variant of Alzheimer's disease. In this paper, in situ atomic force microscopy has been used to study the structural properties of alpha-synuclein fibrils in solution using two different atomic force microscopy imaging modes: tapping mode and contact mode. In the in situ contact mode atomic force microscopy experiments alpha-synuclein fibrils quickly broke into fragments, and a similar phenomenon was found using tapping mode atomic force microscopy in which alpha-synuclein fibrils were incubated with guanidine hydrochloride (0.6 M). The alpha-synuclein fibrils kept their original filamentous topography for over 1 h in the in situ tapping mode atomic force microscopy experiments. The present results provide indirect evidence on how beta-sheets assemble into alpha-synuclein fibrils on a nanometer scale.
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ji
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Hu
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Xu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: He
mesh_terms: D019791:Guanidine / Q000494:pharmacology; D018625:Microscopy, Atomic Force; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D011489:Protein Denaturation / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D013314:Stress, Mechanical; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D019791:Guanidine