Effects of Anti-Alzheimer Drugs on Phosphorylation and Assembly of Microtubules from Brain Microtubular Proteins

被引：7

作者：

Shevtsov, P. N. ^{[1
]}

Shevtsova, E. F. ^{[2
]}

Burbaeva, G. Sh. ^{[1
]}

Bachurin, S. O. ^{[2
]}

机构：

[1] Russian Acad Med Sci, Mental Hlth Res Ctr, Lab Neurochem, Moscow 109801, Russia

[2] Russian Acad Med Sci, Inst Physiol Act Subst, Lab Neurochem, Moscow, Russia

来源：

BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE | 2014年 / 156卷 / 06期

关键词：

microtubules; Alzheimer's disease; tacrine; amiridine; memantine; DISEASE; TRIAZOLAM; TACRINE;

D O I：

10.1007/s10517-014-2445-9

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

We studied the effects of anti-Alzheimer drugs (tacrine, amiridine, and memantine) on phosphorylation of tubulin and microtubule-associated proteins isolated from rat brain, evaluated the capacity of these proteins to polymerize into microtubules after addition of study pharmacological agents, and analyzed the structure of generated microtubules. It was shown that test substances impair assembly of microtubules to a different extent. Dose-dependent effects of these agents on phosphorylation of tubulin and microtubule-associated proteins were observed. Triazolam (not approved for clinical use as anti-Alzheimer drug) in the same concentrations was used as the reference substance in the same tests. It was observed that this substance even in minimal concentration induced the most pronounced changes in microtubule structure. A direct correlation between the capacity of the test substances to modulate tubulin phosphorylation and to impair microtubule structure was found: the more the substance inhibited tubulin phosphorylation, the more it disordered microtubule structure.

引用

页码：768 / 772

页数：5

共 15 条

[1] The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer's disease and related tauopathies [J].

Brunden, Kurt R. ;

Yao, Yuemang ;

Potuzak, Justin S. ;

Ferrer, Nuria Ibarz ;

Ballatore, Carlo ;

James, Michael J. ;

Hogan, Anne-Marie L. ;

Trojanowski, John Q. ;

Smith, Amos B., III ;

Lee, Virginia M. -Y. .

PHARMACOLOGICAL RESEARCH, 2011, 63 (04) :341-351

[2] A DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TACRINE FOR ALZHEIMERS-DISEASE [J].

DAVIS, KL ;

THAL, LJ ;

GAMZU, ER ;

DAVIS, CS ;

WOOLSON, RF ;

GRACON, SI ;

DRACHMAN, DA ;

SCHNEIDER, LS ;

WHITEHOUSE, PJ ;

HOOVER, TM ;

MORRIS, JC ;

KAWAS, CH ;

KNOPMAN, DS ;

EARL, NL ;

KUMAR, V ;

DOODY, RS .

NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (18) :1253-1259

[3] Alzheimer's disease : from brain lesions to new drugs [J].

Forette, Francoise ;

Hauw, Jean-Jacques .

BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE, 2008, 192 (02) :363-380

[4]

Gavrilova S. I., 2001, NEURODEGENERATIVE DI

[5]

Gavrilova S. I., 2003, PHARMACOTHERAPY ALZH

[6]

HutterPaier B, 1996, J NEURAL TRANSM-SUPP, P276

[7] Tau in Alzheimer Disease and Related Tauopathies [J].

Iqbal, K. ;

Liu, F. ;

Gong, C. -X. ;

Grundke-Iqbal, I. .

CURRENT ALZHEIMER RESEARCH, 2010, 7 (08) :656-664

[8] MICROTUBULES AND MICROTUBULE-ASSOCIATED PROTEINS [J].

MANDELKOW, E ;

MANDELKOW, EM .

CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (01) :72-81

[9] HYPOTHESIS - MICROTUBULES, A KEY TO ALZHEIMER-DISEASE [J].

MATSUYAMA, SS ;

JARVIK, LF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) :8152-8156

[10] TRIAZOLAM IN ALZHEIMERS-DISEASE - PILOT-STUDY ON SLEEP AND MEMORY EFFECTS [J].

MCCARTEN, JR ;

KOVERA, C ;

MADDOX, MK ;

CLEARY, JP .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1995, 52 (02) :447-452

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