Neuroprotective properties of mildronate, a mitochondria-targeted small molecule

Jolanta Pupure, Sergejs Isajevs, Elina Skapare, Juris Rumaks, Simons Svirskis, Darja Svirina, Ivars Kalvinsh, Vija Klusa

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Mildronate, a representative of the aza-butyrobetaine class of drugs with proven cardioprotective efficacy, was recently found to prevent dysfunction of complex I in rat liver mitochondria. The present study demonstrates that mildronate also acts as a neuroprotective agent. In a mouse model of azidothymidine (anti-HIV drug) neurotoxicity, mildronate reduced the azidothymidine-induced alterations in mouse brain tissue: it normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression assessed by quantitative and semi-quantitative analysis. Mildronate also normalized the changes in cytochrome c oxidase (COX) expression, reduced the expression of glial fibrillary acidic protein (GFAP) and cellular infiltration. The present results show that the neuroprotective action of mildronate results at least partially from anti-neurodegenerative (anti-apoptotic) and anti-inflammatory mechanisms. It might be suggested that the molecular conformation of mildronate can facilitate its easy binding to mitochondria, and regulate the expression of different signal molecules, hence maintaining cellular signaling and survival.

Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalNeuroscience Letters
Issue number2
Publication statusPublished - 12 Feb 2010
Externally publishedYes


  • Azidothymidine neurotoxicity
  • Mildronate
  • Neurodegeneration
  • Neuroinflammation
  • Neuroprotection

Field of Science*

  • 3.2 Clinical medicine
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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