Title:New Therapeutic Property of Dimebon as a Neuroprotective Agent
VOLUME: 25 ISSUE: 39
Author(s):Aleksey Ustyugov, Elena Shevtsova, Ghulam Md Ashraf, Vadim V. Tarasov, Sergey O. Bachurin and Gjumrakch Aliev*
Affiliation: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
Keywords:Dimebon, Latrepirdine, proteinopathy, neuroprotection, mitochondrial permeability transition, neurodegenerative
disorders.
Abstract: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.
