title: Dynamic structural flexibility of α-synuclein.
abstract: α-Synuclein is a conserved, abundantly expressed protein that is partially localized in pre-synaptic terminals in the central nervous system. The precise biological function(s) and structure of α-synuclein are under investigation. Recently, the native conformation and the presence of naturally occurring multimeric assemblies have come under debate. These are important deliberations because α-synuclein assembles into highly organized amyloid-like fibrils and non-amyloid amorphous aggregates that constitute the neuronal inclusions in Parkinson's disease and related disorders. Therefore understanding the nature of the native and pathological conformations is pivotal from the standpoint of therapeutic interventions that could maintain α-synuclein in its physiological state. In this review, we will discuss the existing evidence that define the physiological states of α-synuclein and highlight how the inherent structural flexibility of this protein may be important in health and disease.
authors.affiliation: Biomedical graduate studies in Neuroscience, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Mor
authors.affiliation: Biomedical graduate studies in Biochemistry and Molecular Biophysics, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Ugras
authors.affiliation: Biomedical graduate studies in Pharmacology, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Daniels
authors.affiliation: Biomedical graduate studies in Neuroscience, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States; Biomedical graduate studies in Biochemistry and Molecular Biophysics, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States; Biomedical graduate studies in Pharmacology, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States; Children's Hospital of Philadelphia Research Institute, PA 19104, United States; Department of Pediatrics, Raymond, and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States; Department of Systems Pharmacology and Translational Therapeutics, Raymond, and Ruth Perelman School of Medicine at the University of Pennsylvania, PA 19104, United States. Electronic address: ischirop@mail.med.upenn.edu.
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000818:Animals; D006801:Humans; D008956:Models, Chemical; D017711:Nonlinear Dynamics; D011487:Protein Conformation; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein