Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death

  • Zhang S
  • Hedskog L
  • Petersen C
 et al. 
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Abstract

Dimebon, a drug currently being evaluated in multiple Phase III Alzheimer's disease trials, has previously been shown to have effects on isolated mitochondria at muM concentrations. Here the effects of nM concentrations of Dimebon on mitochondrial function were investigated both in primary mouse cortical neurons and human neuroblastoma cells (SH-SY5Y). Under non-stress conditions nM concentrations of Dimebon increased succinate dehydrogenase activity (MTT-assay), mitochondrial membrane potential (DeltaPsim), and cellular ATP levels. Dimebon treatment had no effect on mitochondria DNA content, implying that mitochondrial biogenesis was not induced. Under stress conditions, mitochondria in Dimebon-treated neurons showed increased resistance to elevated intracellular calcium concentrations, thus, maintaining their DeltaPsim throughout the experiment, in contrast to control neurons, which rapidly lost their DeltaPsim. Moreover, we show that serum-starved differentiated SH-SY5Y cells treated with Dimebon had an increased survival rate as compared to untreated cells. In conclusion, these data demonstrate that Dimebon enhances mitochondrial function both in the absence and presence of stress and Dimebon-treated cells are partially protected to maintain cell viability.

Author-supplied keywords

  • Alzheimer's disease
  • Dimebon (latrepirdine)
  • mitochondria
  • neuronal cells

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Authors

  • Shouting Zhang

  • Louise Hedskog

  • Camilla A.Hansson Petersen

  • Bengt Winblad

  • Maria Ankarcrona

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