α -Synuclein Modification in an ALS Animal Model

Amyotrophic lateral sclerosis (ALS) is a progressively paralytic neurodegenerative disease that can be caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1). Transgenic mice that overexpress mutant SOD1 develop paralysis and accumulate aggregates of mutant protein in the brainstem and spinal cord. Bee venom (BV), which is also known as apitoxin, is extracted from honeybees and is commonly used in oriental medicine for the treatment of chronic rheumatoid arthritis and osteoarthritis. The purpose of the present study was to determine whether BV affects misfolded protein aggregates such as alpha-synuclein, which is a known pathological marker in Parkinson disease, and ubiquitin-proteasomal activity in hSOD1(G93A) mutant mice. BV was bilaterally administered into a 98-day-old hSOD1(G93A) animal model. We found that BV-treated hSOD1(G93A) transgenic mice showed reduced detergent-insoluble polymerization and phosphorylation of α -synuclein. Furthermore, phosphorylated or nitrated α -synuclein was significantly reduced in the spinal cords and brainstems of BV-treated hSOD1(G93A) mice and reduced proteasomal activity was revealed in the brainstems of BV-treated symptomatic hSOD1(G93A). From these findings, we suggest that BV treatment attenuates the dysfunction of the ubiquitin-proteasomal system in a symptomatic hSOD1(G93A) ALS model and may help to slow motor neuron loss caused by misfolded protein aggregates in ALS models.