Effects of anti-Alzheimer drugs on phosphorylation and assembly of microtubules from brain microtubular proteins.
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.
Laboratory of Neurochemistry, Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, Russia, shevt@dio.ru.
P N
PN
Shevtsov
E F
EF
Shevtsova
G Sh
GSh
Burbaeva
S O
SO
Bachurin
D000544:Alzheimer Disease / Q000188:drug therapy*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D008559:Memantine / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D018697:Nootropic Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000494:pharmacology
D000634:Aminoquinolines; D008869:Microtubule-Associated Proteins; D018697:Nootropic Agents; D013619:Tacrine; C049860:amiridine; D008559:Memantine