Effects of different anti-tau antibodies on tau fibrillogenesis: RTA-1 and RTA-2 counteract tau aggregation

• Published in: FEBS letters Vol. 579; no. 6; pp. 1399 - 1404
• Main Authors: Taniguchi, Taizo, Sumida, Miho, Hiraoka, Shuko, Tomoo, Koji, Kakehi, Tomoko, Minoura, Katsuhiko, Sugiyama, Shigeru, Inaka, Koji, Ishida, Toshimasa, Saito, Naoaki, Tanaka, Chikako
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 28-02-2005
• Subjects: Alzheimer disease; Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; CHO Cells; Cricetinae; ELISA; enzyme-linked immunosorbent assay; frontotemporal dementia and Parkinsonism linked to chromosome 17; FTDP-17; Inhibitor; keyhole limpet hemocyanin; KLH; MBD; microtubule-associated protein; microtubule-binding domain; Molecular Sequence Data; neurofibrillary tangle; NFT; Paired helical filament; PHF; Protein Binding - drug effects; Protein Structure, Quaternary - drug effects; Tau; tau Proteins - chemistry; tau Proteins - genetics; tau Proteins - immunology; tau Proteins - metabolism; Tauopathy; thioflavin S; ThS; Tubulin - chemistry; Tubulin - metabolism; AD; Paired helical filament; KLH; Tau; Tauopathy; MBD; PHF; FTDP-17; Inhibitor; NFT; MAP; ThS; ELISA
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.01.039

Tau is the major antigenic component of neurofibrillary pathology in tauopathy, including Alzheimer’s disease. Although conversion of soluble tau to an insoluble polymerized fibrillar form is a key factor in the pathogenesis of tauopathy, the mechanism of the change is unclear and no inhibitors of fibril formation are available. Monoclonal antibodies against the 1st or 2nd repeat of the microtubule binding domain, but not the C-terminal 16 residues, completely inhibited tau aggregation into PHF. Furthermore, they did not inhibit tau-induced tubulin assembly. Thus, they are useful to investigate tau protein conversion and will be useful therapeutic lead materials.