title: Chronic administration of dimebon ameliorates pathology in TauP301S transgenic mice.
abstract: Dimebon belongs to a fast-growing group of "old" drugs that were suggested to be effective for therapy of pathological conditions different from their original targets. Following initial reports of successful Phase II clinical trials for mild-to-moderate Alzheimer's and Huntington's diseases, effects of Dimebon on various neurodegenerative conditions were investigated both in follow-up clinical trials and in various model systems. Although results of Phase III clinical trials carried out so far were disappointing, there is growing body of evidence that this drug can affect neuronal physiology in a way that would be beneficial at particular stages of development of certain types of neurodegeneration. To reveal what molecular and cellular pathological processes might be affected by Dimebon, we tested the ability of this drug to ameliorate pathology in model systems recapitulating particular pathogenic mechanisms involved in the development and progression of neurodegenerative diseases. Here we assessed the ability of Dimebon to modify several prominent features of tauopathies using transgenic tauP301S mice as a model. Chronic treatment with Dimebon was found to partially protect against the progressive decline in motor function and accumulation of tau-positive dystrophic neurons characteristic of tauP301S mice. Similar results were obtained with two further γ-carbolines structurally similar to Dimebon. Our data suggest that Dimebon and Dimebon-like compounds might be considered as drugs possessing disease-modifying activity for diseases with prominent tau pathology.
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Peters
authors.forename: Natalie
authors.initials: N
authors.lastname: Connor-Robson
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Sokolov
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Aksinenko
authors.forename: Michail S
authors.initials: MS
authors.lastname: Kukharsky
authors.forename: Sergey O
authors.initials: SO
authors.lastname: Bachurin
authors.forename: Natalia
authors.initials: N
authors.lastname: Ninkina
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Buchman
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004334:Drug Administration Schedule; D007211:Indoles / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000008:administration & dosage; D024801:Tauopathies / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D007211:Indoles; C558298:Mapt protein, mouse; D018696:Neuroprotective Agents; D016875:tau Proteins; C010119:latrepirdine