Effects of different anti-tau antibodies on tau fibrillogenesis: RTA-1 and RTA-2 counteract tau aggregation.
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.
Taniguchi
Taizo
T
Biosignal Research Center, Kobe University, Kobe, Hyogo 657-8501, Japan. tanigu@kobe-u.ac.jp
Sumida
Miho
M
Hiraoka
Shuko
S
Tomoo
Koji
K
Kakehi
Tomoko
T
Minoura
Katsuhiko
K
Sugiyama
Shigeru
S
Inaka
Koji
K
Ishida
Toshimasa
T
Saito
Naoaki
N
Tanaka
Chikako
C
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D014404:Tubulin; D016875:tau Proteins