title: Structural Characteristics of α-Synuclein Oligomers.
abstract: Oligomeric forms of amyloid aggregates have been detected in the brains and tissues of patients suffering from neurodegenerative disorders such as Parkinson's disease, and it is widely thought that such species are key pathogenic agents in the development and spreading of the disease; however, the study of these species has been proven to be extremely challenging, primarily as a result of their intrinsically transient nature and high levels of heterogeneity. Identifying the structural nature and the details of the mechanisms of formation and interconversion of individual oligomeric species, particularly those with high toxicity, is of fundamental importance not only for understanding the mechanisms of protein misfolding and amyloid aggregation but also for the identification of diagnostic and therapeutic targets. In this review, we will focus on the current knowledge of the multitude of oligomeric forms of α-synuclein that have been reported to date, with particular emphasis on their structural features and possible relationship to other amyloid species, in order to build a clearer understanding of the types of oligomeric species that accumulate during the aggregation of α-synuclein and to develop a comprehensive picture of the misfolding behavior of the protein.
authors.affiliation: Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), Universidad de Zaragoza, Zaragoza, Spain. Electronic address: ncc@unizar.es.
authors.forename: N
authors.initials: N
authors.lastname: Cremades
authors.affiliation: University of Cambridge, Cambridge, United Kingdom.
authors.forename: S W
authors.initials: SW
authors.lastname: Chen
authors.affiliation: University of Cambridge, Cambridge, United Kingdom.
authors.forename: C M
authors.initials: CM
authors.lastname: Dobson
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D004194:Disease; D006801:Humans; D008958:Models, Molecular; D055503:Protein Multimerization; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Amyloid aggregation; Fibril; Interconversion of states; Multiplicity; Oligomer; Protein misfolding pathways; Relationships between amyloid species; Structure