title: Effects of antiparkinsonian agents on β-amyloid and α-synuclein oligomer formation in vitro.
abstract: The aggregation of β-amyloid protein (Aβ) and α-synuclein (αS) are hypothesized to be the key pathogenic event in Alzheimer's disease (AD) and Lewy body diseases (LBD), with oligomeric assemblies thought to be the most neurotoxic. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for patients with AD and LBD. Here, we examined the effects of antiparkinsonian agents (dopamine, levodopa, trihexyphenidyl, selegiline, zonisamide, bromocriptine, peroxide, ropinirole, pramipexole, and entacapone) on the in vitro oligomer formation of Aβ40, Aβ42, and αS using a method of photo-induced cross-linking of unmodified proteins (PICUP), electron microscopy, and atomic force microscopy. The antiparkinsonian agents except for trihexyphenidyl inhibited both Aβ and αS oligomer formations, and, among them, dopamine, levodopa, pramipexole, and entacapone had the stronger in vitro activity. Circular dichroism and thioflavin T(S) assays showed that secondary structures of Aβ and αS assemblies inhibited by antiparkinsonian agents were statistical coil state and that their seeding activities had disappeared. The antiparkinsonian agents could be potential therapeutic agents to prevent or delay AD and LBD progression.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Takasaki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takahashi
authors.forename: Tokuhei
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000187:drug effects*; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments; D051844:alpha-Synuclein / Q000737:chemistry* / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D000978:Antiparkinson Agents; D010446:Peptide Fragments; D051844:alpha-Synuclein
keywords: antiparkinsonian agents; oligomer; α-synuclein; β-amyloid protein