title: In vitro aggregation assays using hyperphosphorylated tau protein.
abstract: Alzheimer's disease is one of a large group of neurodegenerative disorders known as tauopathies that are manifested by the neuronal deposits of hyperphosphorylated tau protein in the form of neurofibrillary tangles (NFTs). The density of NFT correlates well with cognitive impairment and other neurodegenerative symptoms, thus prompting the endeavor of developing tau aggregation-based therapeutics. Thus far, however, tau aggregation assays use recombinant or synthetic tau that is devoid of the pathology-related phosphorylation marks. Here we describe two assays using recombinant, hyperphosphorylated tau as the subject. These assays can be scaled up for high-throughput screens for compounds that can modulate the kinetics or stability of hyperphosphorylated tau aggregates. Novel therapeutics for Alzheimer's disease and other tauopathies can potentially be discovered using hyperphosphorylated tau isoforms.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University.
authors.forename: Dexin
authors.initials: D
authors.lastname: Sui
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University; kuom@msu.edu.
authors.forename: Min-Hao
authors.initials: MH
authors.lastname: Kuo
mesh_terms: D005470:Fluorometry / Q000295:instrumentation / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D010766:Phosphorylation; D066329:Protein Aggregates; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D011994:Recombinant Proteins; D016875:tau Proteins