6533b829fe1ef96bd128a2eb
RESEARCH PRODUCT
Neuroprotective properties of mildronate, a mitochondria-targeted small molecule.
Juris RumaksIvars KalvinshJolanta PupureSimons SvirskisDarja SvirinaVija KlusaSergejs IsajevsElina Skaparesubject
MaleCell signalingAnti-HIV AgentsNitric Oxide Synthase Type IIMice Inbred StrainsMitochondrionPharmacologyNeuroprotectionElectron Transport Complex IVMiceCellular Apoptosis Susceptibility ProteinGlial Fibrillary Acidic ProteinmedicineAnimalsLymphocytesNeuroinflammationGlial fibrillary acidic proteinbiologyCaspase 3General NeuroscienceNeurodegenerationNeurotoxicityBrainmedicine.diseaseDisease Models AnimalNeuroprotective AgentsBiochemistrybiology.proteinNeurotoxicity SyndromesZidovudineCellular apoptosis susceptibility proteinMethylhydrazinesdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-02-01 | Neuroscience letters |