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Dimebon (latrepirdine) Can Ameliorate Different Forms Of Proteinopathy | 21994
ISSN: 2161-0460
Journal of Alzheimers Disease & Parkinsonism
Open Access
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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 ?g/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.
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