1. Institute of Physiologically Active Compounds of Russian Academy of Sciences 2. Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences 3. Institute of Physiologically Active Compounds of Russian Academy of Sciences, Cardiff University, BIOSI3
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.
Download PDF:
Keywords: neurodegeneration, neuroprotection, protein aggregation, transgenic models, dimebon
Citation:
Shelkovnikova T.A., Ustyugov A.A., Kokhan V.S., Tarasova T.V., Medvedeva V.K., Khrytankova I.V., Bachurin S.O., Ninkina N.N. (2014) Study into molecular targets of a neuroprotective compound dimebon using a transgenic mice line. Biomeditsinskaya Khimiya, 60(3), 354-363.
Shelkovnikova T.A. et al. Study into molecular targets of a neuroprotective compound dimebon using a transgenic mice line // Biomeditsinskaya Khimiya. - 2014. - V. 60. -N 3. - P. 354-363.
Shelkovnikova T.A. et al., "Study into molecular targets of a neuroprotective compound dimebon using a transgenic mice line." Biomeditsinskaya Khimiya 60.3 (2014): 354-363.
Shelkovnikova, T. A., Ustyugov, A. A., Kokhan, V. S., Tarasova, T. V., Medvedeva, V. K., Khrytankova, I. V., Bachurin, S. O., Ninkina, N. N. (2014). Study into molecular targets of a neuroprotective compound dimebon using a transgenic mice line. Biomeditsinskaya Khimiya, 60(3), 354-363.
Pieper A.A., Xie S., Capota E. Estill S.J., Zhong J., Long J.M., Becker G.L., Huntington P., Goldman S.E., Shen C.H., Capota M., Britt J.K., Kotti T., Ure K., Brat D.J., Williams N.S., MacMillan K.S., Naidoo J., Melito L., Hsieh J., De Brabander J., Ready J.M., McKnight S.L. (2010) Cell, 142, 39-51. CrossRef Scholar google search
MacMillan K.S., Naidoo J., Liang J., Melito L., Williams N.S., Morlock L., Huntington P.J., Estill S.J., Longgood J., Becker G.L., McKnight S.L., Pieper A.A., De Brabander J.K., Ready J.M. (2011) J. Amer.Chem.Soc., 133, 1428-1437. CrossRef Scholar google search
Vignisse J., Steinbusch H.W., Bolkunov A., Nunes J., Santos A.I., Grandfils C., Bachurin S., Strekalova T. (2011) Progr. Neuropsychopharmacol. Biol. Psychiatry, 35(2), 510-522. CrossRef Scholar google search
Webster S.J., Wilson C.A., Lee C.H., Mohler E.G., Terry A.V. Jr, Buccafusco J.J. (2011) Br. J. Pharmacol., 164, 970-978. CrossRef Scholar google search
Bachurin S., Bukatina E., Lermontova N., Tkachenko S., Afanasiev A., Grigoriev V., Grigorieva I., Ivanov Y., Sablin S., Zefirov N. (2001) Ann. NY Acad. Sci., 939, 425-435. CrossRef Scholar google search
Bachurin S.O., Shevtsova E.P., Kireeva E.G., Oxenkrug G.F., Sablin S.O. (2003) Ann. NY Acad. Sci., 993, 334-344. CrossRef Scholar google search
Zhang S., Hedskog L., Petersen C.A., Winblad B., Ankarcrona A. (2010) J. Alzheimers Dis., 21, 389-402. Scholar google search
