title: New Therapeutic Property of Dimebon as a Neuroprotective Agent.
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.
authors: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, Russian Federation.
authors: Aleksey
authors: A
authors: Ustyugov
authors: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, Russian Federation.
authors: Elena
authors: E
authors: Shevtsova
authors: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Ghulam Md
authors: GM
authors: Ashraf
authors: Sechenov First Moscow State Medical University, 119991, Moscow, Russian Federation.
authors: Vadim V
authors: VV
authors: Tarasov
authors: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, Russian Federation.
authors: Sergey O
authors: SO
authors: Bachurin
authors: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Chernogolovka, 142432, Russian Federation.|Sechenov First Moscow State Medical University, 119991, Moscow, Russian Federation.|GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229, United States.|School of Health Science and Healthcare Administration, University of Atlanta, E. Johns Crossing, #175, Johns Creek, GA, 30097, United States.
authors: Gjumrakch
authors: G
authors: Aliev
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D007211:Indoles; D018696:Neuroprotective Agents; D034702:RNA-Binding Protein FUS; D016875:tau Proteins; C010119:latrepirdine
keywords: Dimebon; Latrepirdine; mitochondrial permeability transition; neurodegenerative
  disorders; neuroprotection; proteinopathy.