Mechanistic Basis of Phenothiazine-Driven Inhibition of Tau Aggregation

被引：115

作者：

Akoury, Elias ^{[1
,2
]}

Pickhardt, Marcus ^{[3
,4
]}

Gajda, Michal ^{[1
]}

Biernat, Jacek ^{[3
,4
]}

Mandelkow, Eckhard ^{[3
,4
]}

Zweckstetter, Markus ^{[1
]}

机构：

[1] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany

[2] Deutsch Zentrum Neurodegenerat Erkrankungen DZNE, D-37077 Gottingen, Germany

[3] German Ctr Neurodegenerat Dis, DZNE, D-53175 Bonn, Germany

[4] CAESAR Res Ctr, D-53175 Bonn, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2013年 / 52卷 / 12期

关键词：

aggregation; Alzheimer's disease; inhibitors; NMR spectroscopy; Tau protein; METHYLENE-BLUE; PROTEIN; DISEASE; DOMAIN;

D O I：

10.1002/anie.201208290

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Blues brothers: Aggregation of the Tau protein is a key event in Alzheimer's disease and Tau aggregation inhibitors are important as potential drugs. Phenothiazines, such as methylene blue and its azure derivatives, have a unique mechanism, specifically modifying the Tau cysteine residues. The modification keeps Tau in a monomeric disordered conformation preventing the formation of filaments and their toxic precursors. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：3511 / 3515

页数：5

共 27 条

[1]

[Anonymous], 2009, ANGEW CHEM INT ED, V48, P1740

[2] Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum [J].

Buchholz, Kathrin ;

Schirmer, R. Heiner ;

Eubel, Jana K. ;

Akoachere, Monique B. ;

Dandekar, Thomas ;

Becker, Katja ;

Gromer, Stephan .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (01) :183-191

[3]

Bulic B., 2009, Angewandte Chemie, V121, P1772

[4]

Cavaliere P., 2012, BIOCHIM BIOPHYS ACTA, V1832, P20

[5] Structure-Activity Relationship of Cyanine Tau Aggregation Inhibitors [J].

Chang, Edward ;

Congdon, Erin E. ;

Honson, Nicolette S. ;

Duff, Karen E. ;

Kuret, Jeff .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (11) :3539-3547

[6]

CULO F, 1991, AGENTS ACTIONS, V34, P424

[7] TAU-PROTEIN FUNCTION IN LIVING CELLS [J].

DRUBIN, DG ;

KIRSCHNER, MW .

JOURNAL OF CELL BIOLOGY, 1986, 103 (06) :2739-2746

[8] Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity [J].

Fatouros, Chronis ;

Pir, Ghulam Jeelani ;

Biernat, Jacek ;

Koushika, Sandhya Padmanabhan ;

Mandelkow, Eckhard ;

Mandelkow, Eva-Maria ;

Schmidt, Enrico ;

Baumeister, Ralf .

HUMAN MOLECULAR GENETICS, 2012, 21 (16) :3587-3603

[9] A century of Alzheimer's disease [J].

Goedert, Michel ;

Spillantini, Maria Grazia .

SCIENCE, 2006, 314 (5800) :777-781

[10] Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].

Hardy, J ;

Selkoe, DJ .

SCIENCE, 2002, 297 (5580) :353-356

← 1 2 3 →