title: Melittin restores proteasome function in an animal model of ALS.
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.
authors.affiliation: Department of Standard Research, Korea Institute of Oriental Medicine, 483 Expo-ro, Yuseong-gu, Daejeon, 305-811, Korea. yej4823@hanmail.net
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Yang
authors.forename: Seon Hwy
authors.initials: SH
authors.lastname: Kim
authors.forename: Sun Choel
authors.initials: SC
authors.lastname: Yang
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Choi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008555:Melitten / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism*; D017510:Protein Folding / Q000187:drug effects; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D008555:Melitten; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D046988:Proteasome Endopeptidase Complex