Neuronal Dysfunction Associated with Cholesterol Deregulation

Annalisa Marcuzzi, Claudia Loganes, Erica Valencic, Elisa Piscianz, Lorenzo Monasta, Sabrine Bilel, Roberta Bortul, Claudio Celeghini, Marina Zweyer, Alberto Tommasini

Research output: Contribution to journalArticlepeer-review

Abstract

Cholesterol metabolism is crucial for cells and, in particular, its biosynthesis in the central nervous system occurs in situ, and its deregulation involves morphological changes that cause functional variations and trigger programmed cell death. The pathogenesis of rare diseases, such as Mevalonate Kinase Deficiency or Smith⁻Lemli⁻Opitz Syndrome, arises due to enzymatic defects in the cholesterol metabolic pathways, resulting in a shortage of downstream products. The most severe clinical manifestations of these diseases appear as neurological defects. Expanding the knowledge of this biological mechanism will be useful for identifying potential targets and preventing neuronal damage. Several studies have demonstrated that deregulation of the cholesterol pathway induces mitochondrial dysfunction as the result of respiratory chain damage. We set out to determine whether mitochondrial damage may be prevented by using protective mitochondria-targeted compounds, such as MitoQ, in a neuronal cell line treated with a statin to induce a biochemical block of the cholesterol pathway. Evidence from the literature suggests that mitochondria play a crucial role in the apoptotic mechanism secondary to blocking the cholesterol pathway. Our study shows that MitoQ, administered as a preventive agent, could counteract the cell damage induced by statins in the early stages, but its protective role fades over time.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume19
Issue number5
DOIs
Publication statusPublished - May 19 2018

Keywords

  • Anticholesteremic Agents/adverse effects
  • Cell Line, Tumor
  • Cholesterol/metabolism
  • Electron Transport
  • Humans
  • Lovastatin/adverse effects
  • Mitochondria/drug effects
  • Neurons/drug effects
  • Neuroprotective Agents/pharmacology
  • Organophosphorus Compounds/pharmacology
  • Ubiquinone/analogs & derivatives

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