Protective effects of isolecanoric acid on neurodegenerative in vitro models

Neuropharmacology. 2016 Feb:101:538-48. doi: 10.1016/j.neuropharm.2015.09.029. Epub 2015 Oct 9.

Abstract

Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS), are neurodegenerative disorders characterized by loss of dopaminergic or motor neurons, respectively. Although understanding of the PD and ALS pathogenesis remains incomplete, increasing evidence from human and animal studies has suggested that aberrant GSK3β, oxidative stress and mitochondrial damage are involved in their pathogenesis. Using two different molecular models, treatment with L-BMAA for ALS and rotenone for PD the effect of isolecanoric acid, a natural product isolated from a fungal culture, was evaluated. Pre-treatment with this molecule caused inhibition of GSK3β and CK1, and a decrease in oxidative stress, mitochondrial damage, apoptosis and cell death. Taken together, these results indicated that isolecanoric acid might have a protective effect against the development of these neurodegenerative disorders.

Keywords: ALS disease; GSK3β; Isolecanoric acid; L-BMAA; Natural products; Neurodegenerative disorders; Parkinson's disease; Rotenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Diamino / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Transformed
  • Cell Survival
  • Cyanobacteria Toxins
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Flow Cytometry
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroblastoma / pathology
  • Neuroprotective Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Salicylates / pharmacology*

Substances

  • Amino Acids, Diamino
  • Cyanobacteria Toxins
  • Excitatory Amino Acid Agonists
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Salicylates
  • beta-N-methylamino-L-alanine
  • lecanoric acid
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3