TY - JOUR
T1 - Novel conformation-sensitive antibodies specific to three- and four-repeat tau
AU - Ueno, Hitomi
AU - Murayama, Ohoshi
AU - Maeda, Sumihiro
AU - Sahara, Naruhiko
AU - Park, Jung Mi
AU - Murayama, Miyuki
AU - Sanda, Akihiro
AU - Iwahashi, Kazuhiko
AU - Matsuda, Motoo
AU - Takashima, Akihiko
N1 - Funding Information:
This work was partially supported by Grant-in-Aid for Scientific Research 11680746 from the Japanese Ministry of Education, Science, and Culture, and by Grant-in-Aid for Matching Fund Subsidy for Private Universities from The Promotion and Mutual Aid Corporation for Private Schools of Japan.
PY - 2007/6/29
Y1 - 2007/6/29
N2 - Two types of tau isoform, three- and four-repeat tau, are found in neurofibrillary tangles-a pathological hallmark of tauopathies. Which isoform is deposited in the affected tissues depends on the tauopathy. To study how and which tau isoforms contribute to neuronal degeneration, we have developed and characterized two novel conformation-sensitive antibodies, T3R and T4R. Two closely related synthetic peptides, PGGGKVQIVYK and PGGGSVQIVYK, respectively, were designed as antigens. The isoform-specific residues, 305K in three-repeat tau or 305S in four-repeat tau, and the PHF6 motif (VQIVYK) were identified as critical sequences. Despite the high similarity of the antigens, there was no cross-reactivity between T3R and T4R. Furthermore, T3R and T4R showed reduced binding to the thioflavin-positive β-structural form of their target. These features may enable these antibodies to act as novel indicators that allow us to observe and evaluate conformational changes in each distinct isoform of tau.
AB - Two types of tau isoform, three- and four-repeat tau, are found in neurofibrillary tangles-a pathological hallmark of tauopathies. Which isoform is deposited in the affected tissues depends on the tauopathy. To study how and which tau isoforms contribute to neuronal degeneration, we have developed and characterized two novel conformation-sensitive antibodies, T3R and T4R. Two closely related synthetic peptides, PGGGKVQIVYK and PGGGSVQIVYK, respectively, were designed as antigens. The isoform-specific residues, 305K in three-repeat tau or 305S in four-repeat tau, and the PHF6 motif (VQIVYK) were identified as critical sequences. Despite the high similarity of the antigens, there was no cross-reactivity between T3R and T4R. Furthermore, T3R and T4R showed reduced binding to the thioflavin-positive β-structural form of their target. These features may enable these antibodies to act as novel indicators that allow us to observe and evaluate conformational changes in each distinct isoform of tau.
KW - Alzheimer's disease
KW - Conformation-dependent antibody
KW - Isoform-specific antibody
KW - PHF6 motif
KW - Tau isoform
KW - Tauopathy
KW - β-Structure
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U2 - 10.1016/j.bbrc.2007.04.176
DO - 10.1016/j.bbrc.2007.04.176
M3 - Article
C2 - 17493585
AN - SCOPUS:34248576194
SN - 0006-291X
VL - 358
SP - 602
EP - 607
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -