title: [Study into molecular targets of a neuroprotective compound dimebon using a transgenic mice line].
abstract: In the present study we have used a transgenic mice overexpressing an amyloidogenic protein, gamma-synuclein, in the nervous system to address the effect of dimebon on proteinopathy progression. Neuroprotective effect of chronic dimebon administration in these mice at organismal level was confirmed by the increased lifespan. Using histological and biochemical approaches we have demonstrated that dimebon reduced the number of amyloid inclusions in spinal cord of transgenic animals and decreased the content of ubiquitinated proteins in detergent-insoluble fractions. These effects are likely to occur at the level of aggregated protein species, since transgene expression was not altered. Thus, pathological protein aggregation serves as one of dimebon targets in neurodegeneration.
authors.forename: T A
authors.initials: TA
authors.lastname: Shelkovnikova
authors.forename: A A
authors.initials: AA
authors.lastname: Ustiugov
authors.forename: V S
authors.initials: VS
authors.lastname: Kokhan
authors.forename: T V
authors.initials: TV
authors.lastname: Tarasova
authors.forename: V K
authors.initials: VK
authors.lastname: Medvedeva
authors.forename: I V
authors.initials: IV
authors.lastname: Khritankova
authors.forename: S O
authors.initials: SO
authors.lastname: Bachurin
authors.forename: N N
authors.initials: NN
authors.lastname: Ninkina
mesh_terms: D000284:Administration, Oral; D000686:Amyloidosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005427:Flocculation; D015870:Gene Expression; D007211:Indoles / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012995:Solubility; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057149:Ubiquitinated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination; D051845:gamma-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D007211:Indoles; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D057149:Ubiquitinated Proteins; D051845:gamma-Synuclein; C010119:latrepirdine
keywords: dimebon; neurodegeneration; neuroprotection; protein aggregation; transgenic models