Disease-modifying neuroprotective action of the agent Dimebon (latrepirdine) in animal models of neurodegeneration

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Bachurin S

RAS, Russian Federation

: J Spine Neurosurg

Abstract

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Dimebon launched in early 80s in Russia as antihistamine agent belongs to a fast-growing group of “old” medicines that were suggested to be effective for therapy of pathological conditions different from their original targets. Here, we overview most recent Dimebon studies on the pathological process in the brain involving in vivo models of proteinopathies where neurodegenerative effects are envisaged by a group of aggregate-prone proteins such as gamma-synuclein, mimic of hyperphosphorylated tau, and FUS which are engaged in numerous neurological diseases. The main focus is on in vitro models comprised of cultured SH-SYS5 neuroblastoma cells expressing mutant forms of TDP-43 and showing reduced number of inclusion-containing cells upon Dimebon treatments with activation of autophagy markers. The Dimebon effect on stabilization of mitochondrial functions by increasing the threshold to nonselective mitochondrial pores opening and increasing the calcium retention capacity of mitochondria, and reducing lipid peroxidation is also discussed. The results presented as well as data from other laboratories in the past year provide grounds for an inquest for re-evaluation of therapeutic potential of Dimebon and its newly designed analogs as promising disease-modifying agents in battle with neurodegenerative disorders. Meanwhile, new data emerges in favor of possible antiaging effect and application of Dimebon for treatments of depression, anxiety and ischemia.The most pronounced effect of Dimebon is observed in treatments starting at an early stage of the disease onset and this is the major fact that should be accounted in planning for clinical trials.

Biography

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