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New therapeutic property of dimebon as a neuroprotective agent

dc.contributor.authorUstyugov A.
dc.contributor.authorShevtsova E.
dc.contributor.authorBarreto G.E.
dc.contributor.authorAshraf G.M.
dc.contributor.authorBachurin S.O.
dc.contributor.authorAliev G.
dc.date.accessioned2020-09-02T22:29:50Z
dc.date.available2020-09-02T22:29:50Z
dc.date.issued2018
dc.identifier10.2174/0929867323666160804122746
dc.identifier.citation25, 39, -
dc.identifier.issn09298673
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6474
dc.descriptionDimebon (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. © 2016 Bentham Science Publishers.
dc.language.isoen
dc.publisherBentham Science Publishers B.V.
dc.subjectDimebon
dc.subjectLatrepirdine
dc.subjectMitochondrial permeability transition
dc.subjectNeuroprotection
dc.subjectProteinopathy
dc.subjectdimebon
dc.subjectDNA
dc.subjectgamma synuclein
dc.subjectneuroprotective agent
dc.subjectRNA binding protein FUS
dc.subjectsynuclein
dc.subjecttau protein
dc.subjectdimebon
dc.subjectindole derivative
dc.subjectneuroprotective agent
dc.subjectRNA binding protein FUS
dc.subjecttau protein
dc.subjectautophagy
dc.subjectcell energy
dc.subjectcell function
dc.subjectdegenerative disease
dc.subjectDNA binding
dc.subjectdrug mechanism
dc.subjectin vitro study
dc.subjectlifespan
dc.subjectlipid peroxidation
dc.subjectmitochondrial permeability
dc.subjectmitochondrion
dc.subjectneuroblastoma cell
dc.subjectneuroblastoma cell line
dc.subjectneuroprotection
dc.subjectnonhuman
dc.subjectReview
dc.subjecttauopathy
dc.subjectanimal
dc.subjectchemistry
dc.subjectdegenerative disease
dc.subjectdrug effect
dc.subjectgenetics
dc.subjecthuman
dc.subjectmetabolism
dc.subjectpathology
dc.subjectAnimals
dc.subjectAutophagy
dc.subjectHumans
dc.subjectIndoles
dc.subjectMitochondria
dc.subjectNeurodegenerative Diseases
dc.subjectNeuroprotective Agents
dc.subjectRNA-Binding Protein FUS
dc.subjecttau Proteins
dc.titleNew therapeutic property of dimebon as a neuroprotective agent
dc.typeReview


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