Melittin restores proteasome function in an animal model of ALS

J Neuroinflammation. 2011 Jun 20:8:69. doi: 10.1186/1742-2094-8-69.

Abstract

Amyotrophic lateral sclerosis (ALS) is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1) in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation.Melittin is a 26 amino acid protein and is one of the components of bee venom which is used in traditional Chinese medicine to inhibit of cancer cell proliferation and is known to have anti-inflammatory and anti-arthritic effects.The purpose of the present study was to determine if melittin could suppress motor neuron loss and protein misfolding in the hSOD1G93A mouse, which is commonly used as a model for inherited ALS. Meltittin was injected at the 'ZuSanLi' (ST36) acupuncture point in the hSOD1G93A animal model. Melittin-treated animals showed a decrease in the number of microglia and in the expression level of phospho-p38 in the spinal cord and brainstem. Interestingly, melittin treatment in symptomatic ALS animals improved motor function and reduced the level of neuron death in the spinal cord when compared to the control group. Furthermore, we found increased of α-synuclein modifications, such as phosphorylation or nitration, in both the brainstem and spinal cord in hSOD1G93A mice. However, melittin treatment reduced α-synuclein misfolding and restored the proteasomal activity in the brainstem and spinal cord of symptomatic hSOD1G93A transgenic mice.Our research suggests a potential functional link between melittin and the inhibition of neuroinflammation in an ALS animal model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / enzymology*
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Behavior, Animal / drug effects
  • Brain Stem / cytology
  • Brain Stem / drug effects
  • Brain Stem / enzymology
  • Brain Stem / pathology
  • Cell Death / drug effects
  • Disease Models, Animal
  • Humans
  • Male
  • Melitten / pharmacology*
  • Melitten / therapeutic use*
  • Mice
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Proteasome Endopeptidase Complex / drug effects*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Folding / drug effects
  • Rotarod Performance Test
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / enzymology
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Survival Rate
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein
  • Melitten
  • SOD1 G93A protein
  • Superoxide Dismutase
  • Proteasome Endopeptidase Complex