Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

There is growing body of evidence that dimebon can affect neuronal physiology in a way that would be beneficial at particular stages of development of certain types of neurodegeneration. The ability of dimebon to ameliorate progression of tauopathies has been tested using in transgenic tauP301S mice. Chronic administration of dimebon was found to partially protect against the progressive decline of motor function and accumulation of tau-positive dystrophic neurons, two main pathogenetic features of this mouse model. Similar results were obtained with two other gamma-carbolines structurally similarcognate to dimebon. In human neuroblastoma cells SH-SY5Y, all three compounds were able to stimulate activated expression of autophagy markers. Tin parallel, the effects of dimebon on protein aggregation were also studied in a mouse model of gamma-synucleinopathy was studied. Experimental transgenic animals received Dimebon (10 μg/ml in drinking water) either before the onset of signs of neuronal pathology or when these signs were obvious. Administration of dimebon significantly delayed the development of pathology in both groups, reduced the number of Congo Red-positive amyloid inclusions in the spinal cord and decreased the level of neuroinflammation that accompanied neurodegeneration. It was analyzed the effects of dimebon in vitro on the aggregation of another aggregate-prone protein, TDP-43 in vitro. In cell cultures transfected with truncated forms of TDP-43 that exhibit an increased tendency to aggregate, dimebon reduced the number of TDP-43 positive intracellular inclusions. These data show that dimebon and its derivates can significantly ameliorate progression of different forms of proteinopathy and therefore might have a disease-modifying effect.

Biography

Bachurin Shas completed his PhD from Moscow State University in 1980 and was elected as a personal member of Russian Academy of Science in 2003. He is the head of Medicinal and Biological Chemistry Department of the Institute of Physiologically Active Compounds RAS. He has published more than 100 papers in reputed journals and serving as an editorial board member of repute. He is the author of more than 30 patents on novel biologically active compounds.