Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells

Int J Mol Sci. 2022 Aug 16;23(16):9186. doi: 10.3390/ijms23169186.


Introduction: Alpha lipoic acid (ALA) is a sulphur-containing organic compound, derived from octanoic acid, and an important cofactor for mitochondrial respiratory enzymes. It has strong antioxidant properties that improve mitochondrial function. We investigated if ALA improves mitochondrial dysfunction in a cellular model of Alzheimer's disease (AD).

Methods: SH-SY5Y-APP695 cells were used as a model for an early stage of AD. Vector-transfected SH-SY5Y-MOCK cells served as controls. Using these cells, we investigated mitochondrial respiration (OXPHOS), mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) production, and citrate synthase activity (CS) in cells treated with ALA. Cells were treated for 24 h with different concentrations of ALA and with or without the complex I inhibitor rotenone.

Results: Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells. MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells. ALA treatment showed significant differences in respiration chain complex activities in SH-SY5Y-MOCK cells. Citrate synthase activity was unaffected. ROS levels were significantly lower in both cell lines treated with ALA.

Conclusions: ALA increased the activity of the different complexes of the respiratory chain, and consequently enhanced the MMP, leading to increased ATP levels indicating improved mitochondrial function. ALA only marginally protects from additional rotenone-induced mitochondrial stress.

Keywords: Alzheimer disease; ROS; alpha lipoic acid; mitochondria; mitochondria dysfunction; respiratory chain.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Cell Line, Tumor
  • Citrate (si)-Synthase / metabolism
  • Humans
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism
  • Neuroblastoma* / metabolism
  • Oxidation-Reduction
  • Rotenone / metabolism
  • Rotenone / pharmacology
  • Thioctic Acid* / metabolism
  • Thioctic Acid* / pharmacology


  • Rotenone
  • Thioctic Acid
  • Adenosine Triphosphate
  • Citrate (si)-Synthase

Grant support

This research received no external funding.