Aleksey Ustyugov, Elena Shevtsova, Ghulam Md Ashraf, Vadim V. Tarasov, Sergey O. Bachurin and Gjumrakch Aliev* Pages 5315 - 5326 ( 12 )
Dimebon (or Latrepirdine) was initially used as an anti-histamergic drug but later new therapeutic properties were rediscovered, adding to a growing body of “old” agents with prominent neuroprotective effects. In the present manuscript, we are focusing on our latest study on Dimebon with regard to brain’s pathological processes using in vivo proteinopathy models. In the study, neurodegenerative pathology has been attributed to a group of aggregate-prone proteins: hyperphosphorylated tau, fused in sarcoma and γ-synuclein , which are involved in a number of neurological disorders. We have also presented our in vitro model based on overexpression of an aberrant mutant form of transactive response DNA binding 43 kDa protein in cultured SH-SY5Y neuroblastoma cells. Dimebon treatment followed by the activation of autophagy markers resulted in reduced number of inclusion containing cells. The most significant effects of Dimebon appeared to be on the improving cellular energy balance, mitochondria stability by increasing the threshold for nonselective mitochondrial pore opening as well as on increased calcium retention capacity while reducing lipid peroxidation. The therapeutic potential of Dimebon and newly designed analogs show disease modifying properties and could be used to treat neurodegenerative disorders. In addition, new data hint on a possible anti-aging effect and potential application of Dimebon for treatment of anxiety, ischemia and depression. Overall, our findings suggest that the most pronounced effect of Dimebon was observed when treatment was started at the early stages of disease onset and this factor needs to be taken into account while planning future clinical trials.
Dimebon, Latrepirdine, proteinopathy, neuroprotection, mitochondrial permeability transition, neurodegenerative disorders.
Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Sechenov First Moscow State Medical University, 119991, Moscow, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432