title: n-butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1G93Amouse model of amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1G93Amouse model of amyotrophic lateral sclerosis and explore the possible mechanisms.
  
  
  METHODS
  The SOD1G93Amice were treated by oral administration of BP (q.d., 400 mg/kg d) starting from 60 days of age and continuing until death. The rotarod test was performed to assess the disease onset. The expression levels of apoptosis-related proteins, inflammatory molecules, and autophagy-associated proteins were determined. The number of apoptotic motor neurons and the extent of microglial and astroglial activation were also assessed in the lumbar spinal cords of BP-treated mice. Grip strength test, hematoxylin-eosin staining, nicotinamide adenine dinucleotide hydrogen staining, and malondialdehyde assay were conducted to evaluate the muscle function and pathology.
  
  
  RESULTS
  Although BP treatment did not delay the disease onset, it prolonged the life span and thereafter extended the disease duration in SOD1G93Amouse model of ALS. BP treatment also reduced the motor neuron loss through inhibiting apoptosis. We further demonstrated that the neuroprotective effects of BP might be resulted from the inhibition of inflammatory, oxidative stress, and autophagy.
  
  
  CONCLUSIONS
  Our study suggests that BP may be a promising candidate for the treatment of ALS.
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qin-Ming
authors.initials: QM
authors.lastname: Zhou
authors.affiliation: Liaoning Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.|Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Liaoning Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.|Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Liaoning Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.|Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.|Collaborative Innovation Center for Brain Science, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Wei-Dong
authors.identifier: http://orcid.org/0000-0001-7459-2705
authors.initials: WD
authors.lastname: Le
mesh_terms: D000284:Administration, Oral; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D011897:Random Allocation; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D010796:Phthalic Anhydrides; C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1; C026105:butylidenephthalide
keywords: amyotrophic lateral sclerosis; apoptosis; inflammation; n-butylidenephthalide; oxidative stress